Search Results
within category "Women's Health / OB-GYN"
Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
FFNP-PET/MR Imaging of Progesterone Receptor Expression in Invasive Breast Cancer
The goal of this research is to test the accuracy of PET/MRI imaging with
18F-fluorofuranylnorprogesterone (FFNP) for measuring progesterone receptor (PR) expression
in patients with invasive breast cancer. The hypothesis is that FFNP SUVmax from PET/MRI will
correlate well against the semi-quantitative PR immunohistochemistry score.
Amy Fowler, MD, PhD
Female
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03212170
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Women 18 years of age or older
• Diagnosis of biopsy-proven invasive breast cancer measuring at least 1.0 cm in
diameter by any imaging modality
• Biopsy-proven PR-positive or PR-negative invasive breast cancer
• Undergoing diagnostic breast MRI ordered by the referring clinician for staging and
extent of disease
Exclusion Criteria:
• Inability or unwillingness to provide informed consent to the study
• Participants currently undergoing neoadjuvant chemotherapy/endocrine therapy or those
who have received chemotherapy/endocrine therapy within 6 months prior to the MRI
• Participants who have had neoadjuvant chemotherapy/endocrine therapy, surgical
intervention, or radiation for the current biopsy-proven malignancy
• Participants with breast expanders
• Participants who are or might be pregnant or lactating
• Participants with a contraindication to gadolinium based contrast agents, including
allergy or impaired renal function (per University of Wisconsin Health Guidelines)
• Participants with a history of allergic reaction attributable to compounds of similar
chemical or biologic composition to FFNP
• Participants in liver failure as judged by the patient's physician
• Participants with standard contraindications to MRI, including claustrophobia and
metallic implants incompatible with MRI
• Participants requiring intravenous (IV) conscious sedation for imaging are not
eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be
allowed to participate as long as the following criteria are met:
• The subject has their own prescription for the medication
• The informed consent process is conducted prior to the self-administration of
this medication
• They come to the research visit with a driver
• Participants unable to lie prone for 30 minutes for imaging
FES Imaging to Optimize Tamoxifen for Metastatic Breast Cancer
Despite broad advancements in endocrine therapy for ERα+ breast cancer, resistance ultimately
develops. A common driver of resistance are known ESR1 mutations that lead to constitutively
active receptor signaling and transcriptional regulation that is always "turned on" despite
the absence of estrogen. Patients with ESR1 mutations are expected to have decreased binding
affinity for tamoxifen and thus may be underdosed on standard therapy. [18F]-fluoroestradiol
Positron Emission Tomography/Computed tomography (FES-PET/CT) imaging is a novel functional
imaging technique that can non-invasively measure ERα expression and inhibition in metastatic
ERα+ breast cancer. The proposed a pilot study uses FES-PET/CT imaging to measure ERα
blockade to determine the optimal dose of tamoxifen in patients with ESR1 mutations.
Kari Wisinski, MD
All
19 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT04174352
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Participants must have histologically confirmed breast cancer that is metastatic or
unresectable with the following:
• Estrogen receptor expression by immunohistochemistry greater than or equal to 10%
• ESR1 mutation identified using a Clinical Laboratory Improvement Amendments
(CLIA) certified assay via tumor biopsy tissue or circulating free DNA (cfDNA)
• human epidermal growth factor receptor 2 (HER2) negative
• Participants must have measurable disease as defined by RECIST 1.1 or evaluable bone
disease with at least one lesion measuring 10 mm or greater in size. (Participants
with bone and non-bone disease are eligible. One disease site must meet either the
measurable or evaluable criteria outlined.) Participants with liver-only disease are
not eligible due to the inherent hepatic uptake related to the radiopharmaceutical's
hepatobiliary route of elimination.
• Participants must have received at least 1 prior line of endocrine therapy in the
metastatic setting or have had progression within 12 months of adjuvant endocrine
therapy. Prior Tamoxifen is allowed in any setting. Prior CDK4/6 in the metastatic
setting per NCCN guidelines is allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (See Appendix A)
• Life expectancy of greater than 12 weeks.
• Ability to take oral medications.
• Informed consent: participant must be informed of the investigational nature of the
study and must be able to sign a written informed consent.
• Participants with central nervous system (CNS) metastases must be stable after therapy
for CNS metastases (such as surgery, radiation, or stereotactic radiosurgery) for at
least 1 month.
• Participants must have adequate normal organ and bone marrow function as defined
below:
• Absolute neutrophil count >/= 1,000/mcL
• Hemoglobin >/= 9.0 g/dL
• Platelets >/= 100,000/mcL
• Total bilirubin = 1.5 x upper limit of normal (ULN)
• AST (SGOT)/ ALT (SGPT) = 2.5 x ULN; = 5 x ULN in the setting of metastatic
liver disease
• Creatinine = 1.5 x ULN or creatinine clearance >/= 50 mL/min
Exclusion Criteria:
• Prior chemotherapy, radiotherapy, targeted, immunotherapy or investigational therapy
within 2 weeks or major surgery within 4 weeks of study enrollment or those who have
not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events
due to agents administered more than 2 weeks earlier (alopecia and fatigue excluded).
• Participants must not be receiving an ER blocking endocrine therapy (includes
fulvestrant, tamoxifen, toremifene, raloxifene) and must be off the agents for a
minimum of 60 days prior to planned FES PET/CT to allow for adequate uptake of FES.
• History of allergic reactions attributed to compounds of chemical or biologic
composition similar to those of tamoxifen or [18F]-fluoroestradiol.
• Peripheral neuropathy of severity greater than grade 1.
• Current optic nerve disorders, retinopathy, lattice degeneration, macular
degeneration, retinal vascular disorder, or retinal tears of severity greater than
grade 1.
• History of cerebellar disorders, ataxia, and uncontrolled seizures unless related to
transient medical condition and in investigator's opinion is not an active medical
issue.
• History of venous thrombosis/thromboembolic event, including pulmonary embolism and
stroke.
• Have a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 470msec
or other factors that increase the risk of QT prolongation or arrhythmic events (e.g.,
heart failure, chronic hypokalemia, family history of long QT interval syndrome).
• Are taking medications that are known to prolong the QT interval, unless they can be
transferred to other medications ≥ 5 half-lives prior to dosing or unless the
medications can be properly monitored during the study. If equivalent medication is
not available, QTcF should be closely monitored.
• Tamoxifen has demonstrated vaginal bleeding, birth defects and fetal loss in pregnant
women. Tamoxifen use during pregnancy may have a potential long-term risk to the fetus
of a Diethylstilbestrol syndrome (DES)-like syndrome. Women of childbearing potential
(WOCP) must not be pregnant (confirmed by a negative urine/serum pregnancy test within
14 days of tamoxifen treatment). In addition, a medically acceptable method of birth
control must be used such as an intrauterine device (IUD), use of a double barrier
method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or
cream), or total abstinence during the study participation and for 3 months after last
dose of study drug. Women who are postmenopausal for at least 1 year or surgically
sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not
considered to be WOCP.
• Ongoing treatment with other investigational agents. Participants cannot be receiving
concomitant chemotherapy, radiotherapy, experimental therapy or any other therapy not
otherwise outlined by the trial for the purposes of anti-cancer treatment.
• History of uterine malignancy unless participant has had hysterectomy with no evidence
recurrent disease for ≥ 3 years from definitive therapy.
• Concurrent malignancy except for the following:
• Basal cell or squamous cell skin cancer
• In situ cervical cancer
• The following medications are contraindicated or must be used with caution.
• Contraindicated:
• CYP2D6, CYP3A4, and CYP2C9 strong inhibitors
• CYP2D6, CYP3A4, and CYP2C9 strong inducers
• Use with caution:
• CYP2C9 sensitive substrates
• CYP2D6 moderate inhibitors or inducers
• CYP3A4 moderate inhibitors or inducers
Note: Transdermal products designed for systemic delivery must be assessed for interaction
potential. Topical products not designed to provide systemic delivery (including inhaled
products, ophthalmologic products and transvaginal preparations) do not need to be
considered.
Contraindicated medications are not allowed. Participants taking these concurrent
medications are ineligible unless they can discontinue or switch to alternative medications
prior to initiation of study drug (at least 5 half-lives).
Use with caution agents are permitted if a) discontinuation is not feasible or b) no
acceptable alternatives are available as determined by the treating physician; however,
caution should be used. Consider monitoring by symptoms, labs or drug levels and dose
adjustments of the medication.
• Uncontrolled intercurrent clinically significant illness including, but not limited
to, ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.
Immunonutrition and Carbohydrate Loading Strategies in Breast Reconstruction
This study is designed to test the following hypothesis: patients undergoing immediate
alloplastic and autologous breast reconstruction following mastectomy that receive
preoperative immunonutrition will experience a reduction in wound complications in the 30-day
postoperative period compared to a standard of care control group (retrospective chart
review) of 264 (132 alloplastic + 132 autologous) consecutive breast reconstruction patients
prior to 5/25/2018.
Katherine Gast
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03764943
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Medically cleared to undergo oncologic resection and breast reconstructive surgery
(including associated anesthesia) at the University of Wisconsin Hospital
• Undergoing unilateral or bilateral immediate alloplastic or autologous breast
reconstruction by Drs. Afifi, Garland, Gast, Michelotti, Poore, Rao, or Siebert
Exclusion Criteria:
• Pregnant or breast-feeding women
• Incarcerated women
• Males
• Individuals unable to give consent due to another condition such as impaired
decision-making capacity
• Women with intolerance or allergy to any ingredients contained within the Impact
Advanced Recovery formula that prevents safe consumption of this product.
• Impact Advanced Recovery is suitable for lactose intolerance, gluten-free,
kosher, and halal diets.
• We will exclude individuals with galactosemia
• Women who are unable to take oral nutritional supplements
Breast, Wound Complication, Wound Heal, Complications Wound, Surgical Wound Infection, Surgical Site Infection, Breast Cancer, Mastectomy, Lymphedema
Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy
Eligible subjects will be assigned to study treatment arms by their treating oncologist,
rather than by the study. The drug, dose, and schedule of administration will be determined
by the treating physician per NCCN guidelines for standard of care chemotherapy regimens for
recurrent or metastatic breast cancer. Study treatment arms include: Taxane (nab-paclitaxel
or paclitaxel), Eribulin, Vinorelbine, Ixabepilone, or the control arm (non-microtubule
targeted chemotherapies such as doxorubicin, carboplatin, or gemcitabine).
Mark Burkard, MD, PhD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT03393741
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Men and women with histologically or cytologically demonstrated breast cancer that is
deemed metastatic or incurable by the treating physician.
• It is medically appropriate to treat the patient with an antimitotic agent or an
intravenous control chemotherapeutic agent by IV infusion at standard doses as per the
treating physician. Please see NCCN guidelines for standard of care, p58 for standard
chemotherapy regimens for recurrent or metastatic breast cancer7.
• The patient has measureable disease as determined by RECIST 1.1.
• Archived tissue is available from either primary, metastatic site or both.
• It is safe and feasible to obtain a research tumor biopsy on cycle 1 day 2 with a
biopsy of an accessible lesion such as liver, lung, lymph node, skin, breast, or bone.
• All pre-chemotherapy test results (tests per treating oncologist discretion) have been
reviewed and deemed appropriate for planned chemotherapy by the patient's treating
oncologist.
Exclusion Criteria:
• HER2+ breast cancer by standard criteria.
• Pregnant women are excluded from this study because systemic chemotherapy may cause
deleterious effects to the fetus. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with systemic
chemotherapy, breastfeeding should be discontinued if the mother is enrolled in the
trial.
• Planned treatment with hormonal therapy, or targeted oral therapy during trial
enrollment.
Alpha/Beta CD19+ Depleted Haploidentical Transplantation + Zometa for Pediatric Hematologic Malignancies and Solid Tumors
This phase I trial studies the safety of transplantation with a haploidentical donor
peripheral blood stem cell graft depleted of TCRαβ+ cells and CD19+ cells in conjunction with
the immunomodulating drug, Zoledronate, given in the post-transplant period to treat
pediatric patients with relapsed or refractory hematologic malignancies or high risk solid
tumors.
Christian Capitini, MD
All
7 Months to 21 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT02508038
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
• Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation;
and
• The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi •EIA (Chagas)
Exclusion Criteria:
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
• Lactating females
• Pregnant females
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Syndrome, Rhabdomyosarcoma, Ewing Sarcoma, Primitive Neuroectodermal Tumor, Osteosarcoma, Neuroblastoma, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Ill-Defined Sites, Brain/Central Nervous System, Hematologic cancers, other, Leukemia, Lymphoma, Sarcoma
This is an open label, multi-institutional, single arm phase II trial of ribociclib in
combination with bicalutamide in advanced AR+ triple-negative breast cancer. No randomization
or blinding is involved.
Kari Wisinski, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03090165
Show full eligibility criteria
Hide eligibility criteria
Individuals from populations who are underrepresented in clinical research (e.g., racial
and ethnic minorities, women, individuals from rural/frontier communities, older
individuals) will be enrolled with a goal of ensuring that all eligible patients are given
the opportunity to participate in novel clinical trials and that research findings can be
generalizable to the entire population.
Androgen Receptor (AR) positivity definitions -Phase I: Metastatic or unresectable AR+
triple-negative breast cancer (TNBC); AR positivity defined as IHC staining of >0% of tumor
nuclei.
OR
-Phase II: Metastatic or unresectable AR+ triple-negative breast cancer (TNBC); AR
positivity defined as IHC staining of ≥10% of tumor nuclei.
Inclusion Criteria for Phase I and II study.
In addition to being AR positive as defined in protocol, subjects must also meet all of the
following applicable inclusion criteria.
• Histological or cytological confirmed, metastatic or unresectable triple-negative
breast cancer (TNBC). TNBC will be defined as expression of ER<10%, PR< 10% and HER2
negative either by IHC (0, 1+ are negative, 2+ equivocal) or in situ hybridization
method (ratio <2.0 is negative).
• Written informed consent and HIPAA authorization for release of personal health
information. NOTE: HIPAA authorization may be included in the informed consent or
obtained separately.
• Up to 3 prior line of systemic therapy for metastatic disease is allowed. Combination
therapy will be considered 1 line.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1 or 2 within 28 days prior to registration.
• Life expectancy of > 12 weeks as determined by the treating physician.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• No active central nervous system (CNS) metastatic disease. NOTE: Subjects with CNS
involvement must meet ALL of the following to be eligible:
• At least 28 days from prior definitive treatment of their CNS disease by surgical
resection, stereotactic body radiation therapy (SBRT) or whole brain radiation
treatment (WBRT) at the time of registration
• AND asymptomatic and off systemic corticosteroids and/or enzyme-inducing
anti-epileptic medications for brain metastases for >14 days prior to
registration.
• Prior cancer treatment must be completed at least 14 days prior to registration and
the subject must have recovered from all reversible acute toxic effects of the regimen
(other than alopecia) to ≤grade 1 or to baseline prior to initiation of that therapy.
• Screening rate-corrected QT interval (QTc) must be <450msec and a resting heart rate
of at least 50-90 bpm via a standard 12-lead ECG within 28 days prior to registration.
• Demonstrate adequate bone marrow and organ function as defined in the protocol; all
screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 7
days prior to registration. NOTE: Females are considered of child bearing potential
unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy), or they are naturally postmenopausal for at
least 12 consecutive months, or her male partner has had a vasectomy at least 6 months
prior to screening (The sterilized male partner must be her only sexual partner.).
• Females of childbearing potential and males must be willing to abstain from
heterosexual activity or must agree to use adequate contraception (hormonal or barrier
method) for the duration of study participation and for 3 weeks after discontinuation
of study treatment.
• As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study.
• Able to swallow bicalutamide and ribociclib tablets.
Exclusion Criteria:
• Prior therapy with AR antagonists including but not limited to bicalutamide,
enzalutamide, abiraterone and orteronel.
• Prior therapy with any CDK 4/6 inhibitors with the exception of participation in a
window or preoperative study for Stage I-III operable breast cancer..
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
• Known additional malignancy that is active and/or progressive requiring treatment;
exceptions include basal cell or squamous cell skin cancer, in situ cervical or
bladder cancer, or other cancer for which the subject has been disease-free for at
least three years.
• Treatment with any investigational drug within 14 days prior to registration or within
5 half-lives of the investigational product, whichever is longer. Immunotherapies such
as PD-L1 or PD-1 inhibitors only require a 14 day window, regardless of half-life.
Investigational imaging agents are not included in this definition and are allowed.
• Subject who has received radiotherapy <14 days prior to registration, and who has not
recovered to grade 1 or better from related side effects of such therapy (exceptions
include alopecia and any adverse events deemed by the investigator to be unlikely to
interfere with the study drug safety).
• Subject has had major surgery within 14 days prior to registration or has not
recovered from major side effects of the surgery (tumor biopsy is not considered as
major surgery).
• Known hypersensitivity to any of the excipients of ribociclib or bicalutamide.
• Any impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of HIV infection (testing not mandatory).
• Any concurrent severe and/or uncontrolled medical condition that would, in the
investigator's judgment, cause unacceptable safety risks, contraindicate subject
participation in the clinical study or compromise compliance with the protocol (e.g.
chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled
fungal, bacterial or viral infections, etc.).
• Subjects with any of the following conditions are excluded:
• Serious or non-healing wound, ulcer, or bone fracture.
• History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
abscess within 28 days prior to registration.
• Any history of cerebrovascular accident (CVA) or transient ischemic attack within
12 months prior to registration.
• Any history of arterial or venous thrombosis/thromboembolic event, including
pulmonary embolism within the past 12 months prior to registration.
• History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to registration.
• Symptomatic congestive heart failure (New York Heart Association III-IV) or
documented current cardiomyopathy with left ventricular ejection fraction (LVEF)
<50%
• Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia) or
clinically significant, complete left bundle branch block, high-grade AV block
(e.g. bifascicular block, Mobitz type II and third-degree AV block).
• Any episode of atrial fibrillation in the prior 12 months.
• Long QT syndrome or family history of idiopathic sudden death or congenital long
QT syndrome.
• Concomitant use of medication(s) with a known risk to prolong the QT interval
and/or known to cause Torsades de Pointe that cannot be discontinued (within 5
half-lives or 7 days prior to starting study drug) or replaced by safe
alternative medication. See ManualDocuments/Info tab of the EDC for list of
medications.
• Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening.
• Currently receiving any known strong inducers or inhibitors of CYP3A4/5 which cannot
be discontinued 7 days prior to starting study drug (see Appendix 1 for details).
• Subject is currently receiving or has received systemic corticosteroids <14 days prior
to starting study drugs. The following uses of corticosteroids are permitted: a short
duration (<5 days) of systemic corticosteroidssingle doses, any duration of topical
applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
diseases), eye drops or local injections (e.g., intra-articular).
• Subject is currently receiving warfarin or other coumarin-derived anticoagulant for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH), novel oral anticoagulants (NOACs) or fondaparinux is allowed.
• In subjects with a diagnosis of cirrhosis, sSubjects with a Child-Pugh score B or C
are excluded. Please see chart in the ManualDocuments/Info tab of the electronic data
capture system (EDC) for Child-Pugh score calculation. If subject does not have
diagnosed or suspected cirrhosis, the Child-Pugh score does not need to be calculated.
• Subjects taking herbal supplements (St. John's Wort, gingko balboa, etc.) must
discontinue these supplements 14 days prior to study registration.
• Consumption of grapefruit, grapefruit hybrids, pummelos, star-fruit, Seville oranges
or products containing the juice of each within 7 days prior to study registration.
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors (SPARTA)
To assess:
- efficacy of APL-101 as monotherapy for the treatment of NSCLC harboring MET Exon 14
skipping mutations, NSCLC harboring MET amplification, solid tumors harboring MET
amplification, solid tumors harboring MET fusion, primary CNS tumors harboring MET
alterations, solid tumors harboring wild-type MET with overexpression of HGF and MET
- efficacy of APL-101 as an add-on therapy to EGFR inhibitor for the treatment of NSCLC
harboring EGFR activating mutations and developed acquired resistance with MET
amplification and disease progression after documented CR or PR with 1st line EGFR
inhibitors (EGFR-I)
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03175224
Show full eligibility criteria
Hide eligibility criteria
Major
Inclusion Criteria:
1. Men and women 18 years of age or older.
2. 9 cohorts will be enrolled:
• Cohort A1 / Exon 14 NSCLC MET inhibitor naive in first line: Histologically or
cytologically confirmed NSCLC with Exon 14 skipping mutations; all histologies;
unresectable or metastatic disease (Stage 3b/4); treatment-naive subjects in
first line; not received any MET inhibitor and no known MET kinase inhibitor
resistance mutations
• Cohort A2 / Exon 14 NSCLC •MET inhibitor naïve: Histologically or cytologically
confirmed NSCLC with Exon 14 skipping mutations; all histologies; unresectable or
metastatic disease (Stage 3b/4); pretreated subjects refractory to or intolerant
of standard therapies with no more than three lines of prior therapy in the
unresectable or metastatic setting; not received any MET inhibitor and no known
MET kinase inhibitor resistance mutations
• Cohort B / Exon 14 NSCLC MET inhibitor experienced: ENROLLMENT COMPLETED
• Cohort C / MET amplification basket tumor types excluding primary CNS tumors: Any
solid tumor type regardless of histology excluding primary CNS tumors, with MET
amplification; unresectable or metastatic disease, refractory to or intolerant of
standard therapies, or refused standard therapies, or if therapy was unavailable
or unfeasible, with no more than 3 prior lines of therapy in the unresectable or
metastatic setting; not received any MET inhibitor and no known MET kinase
inhibitor resistance mutations
• Cohort C1 / MET amplification and wild-type EGFR NSCLC: NSCLC regardless of
histology, harboring MET amplification and wild-type EGFR; unresectable or
metastatic disease, previously untreated or treated with no more than 3 prior
lines of therapy in the unresectable or metastatic setting; not received any MET
inhibitor and no known MET kinase inhibitor resistance mutations
• Cohort C2 / EGFR positive NSCLC with acquired MET amplification (APL-101 Add-on
Therapy): Unresectable or metastatic NSCLC regardless of histology, harboring
EGFR activating mutations with acquired MET-Amplification as resistance mechanism
to the EGFR-I; developed resistance to first-line EGFR-inhibitor therapy after an
initial response (documented PR for at least 12 weeks); radiological
documentation of disease progression per RECIST on first-line EGFR inhibitor
therapy; currently on an EGFR-inhibitor therapy and agrees to receive APL-101 as
an add-on therapy during the study; no history of interstitial lung disease
(ILD)/pneumonitis, Grade ≥3 liver toxicity or QT prolongation with EGFR-I
therapy; not received any MET inhibitor and no known MET kinase inhibitor
resistance mutations
• Cohort D / MET fusion basket tumor types excluding primary CNS tumors: any solid
tumor type regardless of histology excluding primary CNS tumors; unresectable or
metastatic disease, refractory to or intolerant of standard therapies, or refused
standard therapies, or if therapy was unavailable or unfeasible, with no more
than 3 prior lines of therapy in the unresectable or metastatic setting; not
received any MET inhibitor and no known MET kinase inhibitor resistance mutations
• Cohort E / Primary CNS tumors with MET alterations: subjects with primary CNS
tumors who meet inclusion criteria of MET dysregulations defined as single or
co-occurred MET fusion including PTPRZ1-MET (ZM) fusion, MET Exon 14 skipping
mutations, or MET amplification; refractory to or intolerant of standard
therapies, or refused standard therapies, or if therapy was unavailable or
unfeasible, with no more than 3 prior lines of therapy in the unresectable or
metastatic setting; not received any MET inhibitor and no known MET kinase
inhibitor resistance mutations; neurological symptoms controlled on a
stable/decreasing dose of steroids for at least 2 weeks before C1D1
• Cohort F / Basket tumor types harboring wild-type MET with over-expression of HGF
and MET: any solid tumor type regardless of histology harboring wild-type MET
with overexpression of HGF and MET; Unresectable or metastatic disease,
refractory to or intolerant of standard therapies, or refused standard therapies,
or if therapy was unavailable or unfeasible, with no more than 3 prior lines of
therapy in the unresectable or metastatic setting; not received any MET inhibitor
and no known MET kinase inhibitor resistance mutations
3. Treated or untreated asymptomatic parenchymal CNS disease or leptomeningeal disease is
allowed.
4. Presence of ≥1 measurable lesion (scan done ≤28 days of C1D1) to serve as target
lesion according to relevant criteria
5. ECOG performance status of 0-1. For subjects with primary CNS tumors, KPS score ≥70.
6. Acceptable organ function
7. For all prior anticancer treatment, a duration of 30 days or 5 half-lives of the
agents used, whichever is shorter, must have elapsed, and any encountered toxicity
must have resolved to levels meeting all the other eligibility criteria prior to the
first dose of study treatment. Palliative radiotherapy to non-target lesions should be
completed within 2 weeks prior to APL-101 administration.
8. Adequate cardiac function
9. Women of child-bearing potential must have a negative serum or Beta-hCG at screening
or evidence of surgical sterility or evidence of post-menopausal status
10. No planned major surgery within 4 weeks of first dose of APL-101
11. Expected survival (life expectancy) ≥ 3 months from C1D1
12. Provision of sample; e.g. archival or a fresh tumor biopsy sample (if safe and
feasible) either from the primary or a metastatic site) or liquid biopsy sample (if
tumor tissue is insufficient or lacking, and approved by the sponsor) is required for
prospective central lab confirmation for study entry (subjects with previously
confirmed molecular status by the Sponsor designated central lab or FDA approved NGS
based MET testing may be exempted, subjected to Sponsor approval.
Major
Exclusion Criteria:
1. Hypersensitivity to APL-101, excipients of the drug product, or other components of
the study treatment regimen.
2. Known actionable mutation/gene rearrangement of EGFR (except for NSCLC subjects in
Cohort C and C-2), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
3. Use or intended use of any other investigational product, including herbal
medications, through Study Treatment Termination.
4. Active uncontrolled systemic bacterial, viral, or fungal infection or clinically
significant, active disease process, which in the opinion of the investigator makes
the risk: benefit unfavorable for the participation of the trial.
5. Life-threatening illness, significant organ system dysfunction or comorbid conditions,
or other reasons that, in the investigator's opinion, could compromise the subject's
safety or the integrity of the study outcomes, or interfere with the absorption or
metabolism of APL-101.
6. Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101,
symptomatic or unstable arrhythmia requiring medical therapy, history of congenital
prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at
screening, or concurrent treatment with a medication that is a known risk for
prolonging the QT interval. Chronic controlled atrial fibrillation is not excluded.
7. Historical seropositive results consistent with active infection for hepatitis C virus
(HCV) or hepatitis B virus (HBV) with high viral loads not actively managed with
antiviral therapy and human immunodeficiency virus (HIV) positive subjects who are not
clinically stable or controlled on their medication (asymptomatic subjects with CD4+
T-cell (CD4+) counts ≥ 350 cells/μL and have not had an opportunistic infection within
the past 12 months prior to first dose of APL-101 would be eligible for study entry.
If history is unclear, relevant test(s) at Screening will be required to confirm
eligibility.
8. Known significant mental illness or other conditions such as active alcohol or other
substance abuse that, in the opinion of the investigator, predisposes the subject to
high risk of noncompliance with the protocol treatment or assessments.
9. Unable to swallow orally administered medication whole.
10. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption
11. Women who are breastfeeding
12. History of another malignancy within 3 years prior to C1D1. A subject with the
following malignancies is allowed if considered cured or unlikely to recur within 3
years:
1. Carcinoma of the skin without melanomatous features.
2. Curatively treated cervical carcinoma in situ.
3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in
situ (T1s), thyroid papillary cancer with prior treatment, prostate cancer which
has been surgically or medically treated and not likely to recur within 3 years.
13. Subjects who are unable or unwilling to discontinue excluded medications (drugs with
known QTc risk and known strong cytochrome P450 [CYP]3A4 inducer and/or strong
inhibitors) for at least 5 half-lives prior to first dose of study drug. Subjects may
qualify if such medication(s) can be safely replaced with alternate medications with
less risk of drug-drug interaction.
14. Subjects with active COVID-19 infection.
15. Symptomatic and/or neurologically unstable CNS metastases, or who require an increase
in steroid dose to control CNS disease. Subjects who have been receiving a stable
steroid dose for at least 2 weeks prior to C1D1 may be allowed.
Solid Tumors, Advanced Cancer, Renal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, NSCLC, Lung Cancer, Brain Tumor, Glioblastoma Multiforme, EGFR Gene Mutation, MET Amplification, HGF, Thyroid Cancer, Pancreatic Cancer, Colon Cancer, MET Alteration, MET Fusion, Exon 14 Skipping, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Letrozole With or Without Paclitaxel and Carboplatin in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
This phase III trial studies how well letrozole with or without paclitaxel and carboplatin
works in treating patients with stage II-IV low-grade serous carcinoma of the ovary,
fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of
estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen
to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different
ways to stop the growth of tumor cells, either by killing the cells, by stopping them from
dividing, or by stopping them from spreading. It is not yet known whether giving letrozole
alone or in combination with paclitaxel and carboplatin works better in treating patients
with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to
paclitaxel and carboplatin without letrozole.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04095364
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must have newly diagnosed, stage II-IV low-grade serous ovarian cancer
(submission of pathology report[s] required). Ovarian cancer = ovarian, fallopian tube
and primary peritoneal cancers
• NOTE: Patients with a prior history of serous borderline tumors but a new
diagnosis of stage II-IV low-grade serous ovarian cancer are eligible
• p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern
(nonaberrant p53 expression is consistent with normal/wildtype TP53)
• A copy of the pathology report that includes the diagnosis of low grade
serous ovarian cancer and nonaberrant p53 IHC result must be submitted in
RAVE. NOTE: If aberrant p53 expression is found on p53 IHC, the patient is
NOT eligible (aberrant p53 expression is consistent with mutant TP53 and
supports diagnosis of high grade serous ovarian cancer)
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 14 days prior to registration;
• Radiographic tumor assessment within 28 days prior to registration. (23-MAY-2023)
• Age >= 18
• Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with
either optimal (=< 1 cm diameter residual disease/nodule) or suboptimal residual
disease (> 1 cm diameter residual disease/nodule) status allowed
• Patients must have undergone a bilateral salpingo-oophorectomy
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0, 1 or 2 within 14 days prior to registration
• Patients must be within =< 8 weeks of primary cytoreductive surgery at time of
randomization
• Patients must be able to take per oral (P.O.) medications
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl (within 14 days
prior to registration)
• Platelets greater than or equal to 100,000 cells/mcl (within 14 days prior to
registration)
• Creatinine less than or equal to 1.5 x upper limit of normal (ULN) (within 14 days
prior to registration)
• Bilirubin less than or equal to 1.5 x ULN (within 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
to 3 x ULN (within 14 days prior to registration)
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
Exclusion Criteria:
• Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy
for the treatment of this disease
• Patients may not have received previous hormonal therapy for the treatment of this
disease
• Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to
carboplatin/paclitaxel therapy
• Patients with severe cardiac disease:
• Myocardial infarction or unstable angina within 6 months prior to registration
• New York Heart Association (NYHA) class II or greater congestive heart failure
• Patients with known central nervous system metastases
• Patients with active (except for uncomplicated urinary tract infection) or
uncontrolled systemic infection
• Patients with >= grade 2 baseline neuropathy
• Known human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months are eligible for
this trial
Low Grade Fallopian Tube Serous Adenocarcinoma, Ovarian Low Grade Serous Adenocarcinoma, Primary Peritoneal Low Grade Serous Adenocarcinoma, Stage II Fallopian Tube Cancer AJCC v8, Stage II Ovarian Cancer AJCC v8, Stage II Primary Peritoneal Cancer AJCC v8, Stage III Fallopian Tube Cancer AJCC v8, Stage III Ovarian Cancer AJCC v8, Stage III Primary Peritoneal Cancer AJCC v8, Stage IV Fallopian Tube Cancer AJCC v8, Stage IV Ovarian Cancer AJCC v8, Stage IV Primary Peritoneal Cancer AJCC v8, Ovary
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual
care that includes regional radiation therapy, with receiving no regional radiation therapy.
Researchers want to see if not giving this type of radiation treatment works as well at
preventing breast cancer from coming back.
Bethany Anderson, MD
Female
35 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03488693
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must be women with newly diagnosed histologically proven invasive carcinoma
of the breast with no evidence of metastases, staged as per site standard of care.
• Patients must have been treated by BCS or mastectomy with clear margins of excision.
Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed.
Multifocal disease (i.e. the presence of two or more foci or breast cancer within the
same breast quadrant) and multicentric disease (i.e. the presence of two or more foci
of breast cancer in different quadrants of the same breast) are allowed.
• Patients with T3N0 disease are eligible.
• Patients with disease limited to nodal micrometastases are eligible
• Patients with nodal macrometastases (>2mm) treated by axillary dissection must have
1-3 positive axillary nodes (macrometastases, > 2 mm).
• Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary
nodes (macrometastases, > 2 mm).
• Patients must be ER ≥ 1% and HER2 negative on local testing
• Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast
tumour tissue from a core biopsy or from the surgical specimen.
• Patient must consent to provision of, and investigator(s) must agree to submit to the
CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour
tissue in order that the specific correlative marker assays described in the protocol
may be conducted
• Patient must consent to provision of samples of blood in order that the specific
correlative marker assays described in the protocol may be conducted.
• Patients must have had endocrine therapy initiated or planned for ≥ 5 years.
Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or
tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine
therapy can be given concurrently or following RT.
• Patients may or may not have had adjuvant chemotherapy.
• RT must commence within 16 weeks of definitive surgery if the patient is not treated
with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks
after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of
randomization). Definitive surgery is defined as the last breast cancer-related
surgery.
• Patient's ECOG performance status must be 0, 1 or 2.
• Patient's age must be ≥ 35 years.
• For the first 736 eligible English or French-speaking subjects who have agreed to
optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and
willing to complete the quality of life, health utilities and lost productivity
questionnaires in either English or French (note: enrollment completed 2022Aug02)
• Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements
• Patients must be accessible for treatment and follow-up. Investigators must assure
themselves the patients randomized on this trial will be available for complete
documentation of the treatment, adverse events, and follow-up.
• In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of
patient randomization.
• Women of childbearing potential must have agreed to use an effective contraceptive
method. A woman is considered to be of "childbearing potential" if she has had menses
at any time in the preceding 12 consecutive months.
Exclusion Criteria:
• Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm).
• Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
• Any prior history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous
or previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer. (Patients with
contralateral DCIS are eligible unless previously treated with radiation.)
• History of non-breast malignancies except adequately treated non-melanoma skin
cancers, in situ cancers treated by local excision or other cancers curatively treated
with no evidence of disease for ≥ 5 years.
• Patients who are pregnant.
• Patients that have had prior ipsilateral chestwall/thoracic radiation.
• Patients treated with chemo or endocrine therapy administered in the neoadjuvant
setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to
surgery is permitted.
• Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.)
which would preclude RT.
• Patients with any serious active or co-morbid medical conditions, laboratory
abnormality, psychiatric illness, active or uncontrolled infections, or serious
illnesses or medical conditions that would prevent the patient from participating or
to be managed according to the protocol (according to investigator's decision).
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients
with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic
alterations that have come back (recurrent) or does not respond to treatment (refractory) and
may have spread from where it first started to nearby tissue, lymph nodes, or distant parts
of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03213652
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have enrolled onto APEC1621SC and must have been given a treatment
assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the
presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study
enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study
enrollment. Patients with neuroblastoma who do not have measurable disease but have
iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in
patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one
dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively
stable for at least 7 days prior to study enrollment; patients who are unable to
walk because of paralysis, but who are up in a wheelchair, will be considered
ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
numerical eligibility criteria are met, e.g. blood count criteria, the patient is
considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
>= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the
last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
growth factors that have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time during which adverse
events are known to occur; the duration of this interval must be discussed with
the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
>= 84 days after infusion and no evidence of graft versus host disease
(GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy
(e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >=
50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s)
being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days
after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment
with other ALK inhibitors is permitted given that at least 5 half-lives or 21
days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to
enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment) (within 7 days
prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided
they meet the blood counts (may receive transfusions provided they are not known to be
refractory to red cell or platelet transfusions); these patients will not be evaluable
for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on
age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for
female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for
female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for
female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL
for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL
for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for
female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT
is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a
written informed consent; assent, when appropriate, will be obtained according to
institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study because there is
currently no available information regarding human fetal or teratogenic toxicities;
pregnancy tests must be obtained in girls who are post-menarchal; males or females of
reproductive potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of study treatment and for one week after the
last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable
or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
not eligible; if used to modify immune adverse events related to prior therapy,
>= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another
investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents
are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong
inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or
inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the
end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors
or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Glioma, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Rhabdomyosarcoma, Recurrent Soft Tissue Sarcoma, Refractory Ependymoma, Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Glioma, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Refractory Soft Tissue Sarcoma, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Kenneth Desantes, M.D.
All
12 Months to 21 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03155620
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Advanced Malignant Solid Neoplasm, Ann Arbor Stage III Non-Hodgkin Lymphoma, Ann Arbor Stage IV Non-Hodgkin Lymphoma, Histiocytic Sarcoma, Juvenile Xanthogranuloma, Langerhans Cell Histiocytosis, Malignant Glioma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Glioma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis, Recurrent Malignant Germ Cell Tumor, Recurrent Malignant Solid Neoplasm, Recurrent Medulloblastoma, Recurrent Neuroblastoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Recurrent Peripheral Primitive Neuroectodermal Tumor, Recurrent Primary Central Nervous System Neoplasm, Recurrent Rhabdoid Tumor, Recurrent Soft Tissue Sarcoma, Refractory Ewing Sarcoma, Refractory Glioma, Refractory Hepatoblastoma, Refractory Langerhans Cell Histiocytosis, Refractory Malignant Germ Cell Tumor, Refractory Malignant Solid Neoplasm, Refractory Medulloblastoma, Refractory Neuroblastoma, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Refractory Peripheral Primitive Neuroectodermal Tumor, Refractory Primary Central Nervous System Neoplasm, Refractory Rhabdoid Tumor, Refractory Rhabdomyosarcoma, Rhabdoid Tumor, Stage III Osteosarcoma AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IV Osteosarcoma AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Osteosarcoma AJCC v7, Stage IVB Osteosarcoma AJCC v7, Wilms Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
This phase III trial studies how well active surveillance help doctors to monitor subjects
with low risk germ cell tumors for recurrence after their tumor is removed. When the germ
cell tumors has spread outside of the organ in which it developed, it is considered
metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. The trial studies
whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic
standard risk germ cell tumors.
Kenneth Desantes, M.D.
All
Not specified
Phase 3
This study is NOT accepting healthy volunteers
NCT03067181
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and
stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I
germ cell tumor; for the standard risk arms, patients must be newly diagnosed with
metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary
extracranial germ cell tumor in any of the categories outlined below is required of
all patients at enrollment except for those who were initially diagnosed with stage I
non-seminoma malignant GCT and later recur during observation post surgery off study;
for these patients, if elevated tumor markers rise to > 5 x upper limit of normal
(ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is
not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk
sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT);
tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage:
COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC)
testicular stage IA, IB and IS; histology: must contain at least one of the following:
yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular
stage IA IB, and IS; histology: must contain at least one of the following: may
contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) <
11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk;
histology: must contain at least one of the following: yolk sac tumor, embryonal
carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op:
alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) <
3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age
(years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the
study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components
of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with
other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac
tumor is the only malignant component present, then it must be deemed by the
pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
(mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L) (within 7 days prior to enrollment)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to
enrollment) AND
• Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol
treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
Exclusion Criteria:
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL
• Pure immature teratoma COG stage II •IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that
contraindicate the use of bleomycin are ineligible for the standard risk arms of the
trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Germ Cell Tumor, Malignant Germ Cell Tumor, Malignant Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage I Ovarian Teratoma AJCC v6 and v7, Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Choriocarcinoma AJCC v6 and v7, Stage I Testicular Embryonal Carcinoma AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7, Stage I Testicular Yolk Sac Tumor AJCC v6 and v7, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage II Testicular Choriocarcinoma AJCC v6 and v7, Stage II Testicular Embryonal Carcinoma AJCC v6 and v7, Stage II Testicular Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Testicular Choriocarcinoma AJCC v6 and v7, Stage III Testicular Embryonal Carcinoma AJCC v6 and v7, Stage III Testicular Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Choriocarcinoma, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Testicular Mixed Choriocarcinoma and Embryonal Carcinoma, Testicular Mixed Choriocarcinoma and Teratoma, Testicular Mixed Choriocarcinoma and Yolk Sac Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Hodgkin's Lymphoma, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with
cancer. Gathering health information over time from younger patients with cancer may help
doctors find better methods of treatment and on-going care.
Kenneth Desantes, M.D.
All
up to 25 Years old
N/A
This study is NOT accepting healthy volunteers
NCT02402244
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Enrollment must occur within 6 months of initial disease presentation OR within 6
months of refractory disease, disease progression, disease recurrence, second or
secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome,
Registry and Future Contact components of APEC14B1 any time after they reach age of
majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent
or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology
(ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in
situ) or three "3" (malignant)
• All neoplastic lesions of the central nervous system regardless of behavior,
i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Neuroendocrine tumors including pheochromocytoma
• Melanocytic tumors, except clearly benign nevi
• Ganglioneuromas
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients
who are being screened specifically for eligibility onto a COG (or COG participating
National Clinical Trials Network [NCTN]) therapeutic study, for which there is a
higher upper age limit
• All patients or their parents or legally authorized representatives must sign a
written informed consent and agree to participate in at least one component of the
study; parents will be asked to sign a separate consent for their own biospecimen
submission
• If patients or their parents or legally authorized representatives have not
signed the Part A subject consent form at the time of a diagnostic bone marrow
procedure, it is recommended that they initially provide consent for drawing
extra bone marrow using the Consent for Collection of Additional Bone Marrow;
consent using the Part A subject consent form must be provided prior to any other
procedures for eligibility screening or banking under APEC14B1
Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neuroendocrine Neoplasm, Stromal Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
Protocol JDI2007-01 is an Expanded Access Protocol with therapeutic 131I-MIBG for patients
with neuroblastoma or pheochromocytoma / paraganglioma, who otherwise do not qualify for
available treatments, or where approved treatment is not commercially available.
Kenneth Desantes, M.D.
All
12 Months and over
Pilot/Feasibility
This study is NOT accepting healthy volunteers
NCT01590680
Show full eligibility criteria
Hide eligibility criteria
INCLUSION CRITERIA:
1. Diagnosis: Refractory or relapsed neuroblastoma with original diagnosis based on tumor
histopathology or elevated urine catecholamines with typical tumor cells in the bone
marrow, OR pheochromocytoma or paraganglioma (less than 12 years of age) not amenable
to curative surgery.
2. Age ≥12 months and able to cooperate with radiation safety restrictions during therapy
period with/without pharmacologic anxiolysis.
3. Disease status: Failure to respond to standard therapy (usually combination
chemotherapy with or without radiation and surgery) or development of progressive
disease at any time (any new lesion or an increase in size of >25% of a pre-existing
lesion). Disease evaluation must be completed within 8 weeks of study entry. If
possible, the disease evaluation should take place subsequent to any intervening
therapy; if intervening therapy does occur, evaluations should be done as clinically
indicated. If patient has received prior treatment with MIBG, they must have a
response or stable disease after the most recent MIBG infusion. Patient may have PD
after showing an initial response to MIBG therapy (at [or around] the day 35-63
post-MIBG therapy evaluation).
4. Stem cells: Patients must have a hematopoietic stem cell product available for
re-infusion after 131I-MIBG treatment at doses of 12 mCi/kg. If no stem cells are
available, then the dose of 131I-MIBG should be <12 mCi/kg.
5. Prior Therapy: Patients may enter this study with or without re-induction therapy for
recurrent tumor. Patients must have fully recovered from the toxic effects of any
prior therapy, meeting the following criteria:
1. At least 2 weeks should have elapsed since any anti-tumor therapy and the patient
must meet certain hematologic criteria.
2. 3 months should have elapsed in the case of completing external beam radiation
for total abdominal, whole lung, total body irradiation (spot irradiation to
skull-based metastases is NOT a contraindication). Patients who receive localized
emergency radiation to sites of life-threatening or function-threatening disease
prior to or immediately after establishment of the definitive diagnosis are not
contraindicated for treatment on this protocol.
3. Cytokine therapy (e.g. G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued
a minimum of 24 hours prior to 131I-MIBG therapy.
4. Minimum of six weeks from previous 131I-MIBG therapy.
5. The lifetime cumulative injected activity should be evaluated by the Investigator
on a case-by-case basis with special attention to any recovery from past
131I-MIBG dose(s).
6. For patients who received a stem cell infusion for a previous 131I-MIBG therapy
but do NOT have remaining stored stem cells:
i. If the stem cell reinfusion was protocol driven but not based upon the development
of profound cytopenias (e.g. automatic stem cell reinfusion on Day 14), the patient is
eligible for retreatment with MIBG at a dose <12 mCi/kg at the investigators
discretion; ii. If the stem cell reinfusion was given based upon the development of
profound cytopenias, decisions for re-treatment with 131I-MIBG will require a
case-by-case evaluation by the Investigator.
6. Organ Function:
1. Liver function: Bilirubin ≤ 2x upper limit of normal; AST/ALT ≤ 10x upper limit
of normal.
2. Kidney function:
i. Serum Creatinine ≤ 2x upper limit of normal OR ii. 24-hr creatinine clearance OR
GFR ≥ 60 ml/min/1.73m2.
c. Hematologic Criteria: ANC ≥750/uL; Platelets ≥ 50,000/uL without transfusion if
stem cells are not available (ANC ≥ 500 and any platelet count allowed if stem cells
available). Patient must be off myeloid growth factors for at least 24 hours. If the
patient has received prior treatment with MIBG, they may be thrombocytopenic, but
requiring no more than 2 platelet transfusions per week to maintain counts above
20,000/uL. Hemoglobin must be ≥ 10gm/dL (transfusion allowed) regardless of stored
stem cell availability.
d. Normal lung function, as manifested by no dyspnea at rest or exercise intolerance,
no oxygen requirement.
e. No clinically significant cardiac dysfunction.
7. Signed informed consent/assent has been obtained.
EXCLUSION CRITERIA:
1. Patients 12 years and older with iobenguane scan positive, unresectable, locally
advanced or metastatic pheochromocytoma or paraganglioma and marketed product is
available.
2. Patients eligible for the Phase II (OPTIMUM) trial.
3. Patients with disease of any major organ system that would compromise their ability to
withstand therapy. Any significant organ impairment should be discussed with the
Principal Investigator prior to patient entry.
4. Because of the teratogenic potential of the study medications, no patients who are
pregnant or lactating will be allowed. Patients of childbearing potential, who are
sexually active, must practice an effective method of birth control while
participating on this study, to avoid possible damage to the fetus . [e.g.
intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with
intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout
the study].
5. Patients who are on hemodialysis
6. Proteinuria, in the absence of urinary infection, within 4 weeks prior to the planned
treatment date is a relative contraindication to receiving therapy for patients with
pheochromocytoma/paraganglioma. Patients with pheochromocytoma/paraganglioma with any
clinically significant proteinuria must have a 24-hr urine protein determination. If
proteinuria is confirmed as being above the institutional upper limit of normal, the
patient is ineligible for MIBG therapy.
7. Patients with active infections that meet grade 3-4 according to the current version
of the NCI CTCAE.
8. Patients with known MIBG-avid parenchymal brain metastases are not eligible. (Patients
with leptomeningeal or skull-based metastases are eligible.)
Neuroblastoma, Pheochromocytoma, Paraganglioma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites
Genetic Analysis in Identifying Late-Occurring Complications in Childhood Cancer Survivors
This clinical trial studies cancer survivors to identify those who are at increased risk of
developing late-occurring complications after undergoing treatment for childhood cancer. A
patient's genes may affect the risk of developing complications, such as congestive heart
failure, avascular necrosis, stroke, and second cancer, years after undergoing cancer
treatment. Genetic studies may help doctors identify survivors of childhood cancer who are
more likely to develop late complications.
Kenneth Desantes, M.D.
All
up to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00082745
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• ELIGIBILITY CRITERIA •CASES
• Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• Development of one of the following key adverse events at any time following
initiation of cancer therapy:
• Cardiac dysfunction; please note: case enrollment has been closed due to
achievement of target accrual
• Ischemic stroke (IS)
• Subsequent malignant neoplasm (SMN)
• Avascular necrosis (AVN); please note: case enrollment has been closed due to
achievement of target accrual
• Submission of a blood specimen (or in certain cases a saliva specimen) to the
Coordinating Center at the University of Alabama at Birmingham as per the
requirements; please note: if a patient is currently receiving active cancer
treatment, it is preferable to obtain the blood sample at a time when the patient's
white blood cell (WBC) is > 2,000
• Written informed consent from the patient and/or the patient's legally authorized
guardian
• In active follow up by a COG institution; active follow up will be defined as date of
last visit or contact by a COG institution within the past 24 months; any type of
contact, including contact specifically for participation in ALTE03N1, qualifies as
active follow-up; please note: treatment on a COG (or legacy group) therapeutic
protocol for the primary cancer is NOT required
• ELIGIBILITY CRITERIA •CONTROLS
• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell
transplant
• CONTROLS: No clinical evidence of any of the following key adverse events:
• Cardiac dysfunction (CD); please note: if a patient is currently receiving active
cancer treatment, it is preferable to obtain the blood sample at a time when the
patient's WBC is > 2,000
• Ischemic stroke (IS)
• Avascular necrosis (AVN)
• Subsequent malignant neoplasm (SMN)
• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to
the Coordinating Center Laboratory at the University of Alabama at Birmingham as per
the requirements
• CONTROLS: Written informed consent from the patient and/or the patient's legally
authorized guardian
• CONTROLS: In active follow up by a COG institution; active follow up will be defined
as date of last visit or contact by a COG institution within the past 24 months; any
type of contact, including contact specifically for participation in ALTE03N1,
qualifies as active follow-up; please note: treatment on a COG (or legacy group)
therapeutic protocol for the primary cancer is NOT required
Childhood Malignant Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia, not otherwise specified, Other Hematopoietic, Ill-Defined Sites, Other
PROMMO Trial: Oral Misoprostol vs IV Oxytocin (PROMMO)
This is a prospective, randomized trial looking at the ideal method of labor induction for
women with prelabor rupture of membranes and an unfavorable cervical Bishop score. The study
will compare oral misoprostol and intravenous oxytocin.
Jacquelyn Adams
Female
18 Years and over
Early Phase 1
This study is also accepting healthy volunteers
NCT04478942
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Early Term to late term pregnancy (>37 weeks and 0 days and <42 weeks and 0 days)
• Late Preterm Pregnancy (34 weeks and 0 days and <37 weeks)
• Confirmed rupture of membranes by either sterile speculum exam or AmniSure
• Simplified Bishop Score ≤ 6
• Maternal Age > 18 years old
• Singleton gestation
• Appropriate gestational age dating by certain LMP or ultrasound performed prior to 20
weeks gestational age
Exclusion Criteria:
• Concern for intra-amniotic infection
• Previous Cesarean delivery
• Lack of appropriate dating criteria for the pregnancy
• Inability to give informed consent in the patient's native language
• Known bleeding disorder such as von Willebrand's disease or hemophilia
• Anticoagulation administration within 24 hours of delivery
Premature Rupture of Membrane, Induction of Labor Affected Fetus / Newborn, Premature rupture of membranes, Other
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric
patients with high-risk neuroblastoma.
Kenneth Desantes, M.D.
All
Not specified
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04023331
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Participant is able and willing to provide informed consent (≥18 years), or informed
consent is obtained by the parent or legal guardian for minor participants, with the
minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has
relapsed or progressed to high-risk, with failure to achieve complete response with
standard therapy (defined as at least 4 cycles of aggressive multi-drug induction
chemotherapy with or without radiation and surgery, or according to a standard
high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to
receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the
Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within
28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet
count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+
cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective
method of birth control while participating on this study, to avoid possible damage to
the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than
that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
1. Participants with disease of any major organ system that would compromise their
ability to tolerate therapy, as deemed by the Investigator or treating
Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance,
oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or
radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the
administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney
within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of
64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior
to the administration of 64Cu-SARTATE), or short acting somatostatin analogues
(administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures
or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned
single or cumulative administered activity is modelled to deliver a radiation dose to
the marrow that exceeds 2 Gy.
Neuroblastoma, Relapsed Neuroblastoma, Refractory Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk)
This clinical trial studies how well two surgical procedures (bilateral salpingectomy and
bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for individuals
with BRCA1 mutations. Bilateral salpingectomy involves the surgical removal of fallopian
tubes, and bilateral salpingo-oophorectomy involves the surgical removal of both the
fallopian tubes and ovaries. This study may help doctors determine if the two surgical
procedures are nearly the same for ovarian cancer risk reduction for women with BRCA1
mutations.
Lisa Barroilhet, MD
Female
35 Years to 50 Years old
N/A
This study is NOT accepting healthy volunteers
NCT04251052
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Individuals 35-50 years of age, inclusive
• Patients who are undergoing risk-reducing salpingo-oophorectomy (RRSO) (for the BSO
arm) and patients who have declined or elected to defer BSO after proper counselling
to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing
salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned
hysterectomy with either arm is permitted
• At least one intact ovary and fallopian tube is in situ at the time of counseling and
consent. Prior hysterectomy is allowed provided it did not include bilateral
salpingectomy. Prior tubal ligation is allowed if one intact ovary and fallopian tube
(with fimbria not removed) are present
• Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for
pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation
of the result is required
• Patients may be premenopausal or menopausal
• Transvaginal ultrasound (TVUS) and CA-125 within 180 days of registration
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Individuals who are currently pregnant or plan to become pregnant in the future
through assisted reproductive technologies and who have received proper counseling are
eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at
the time of a planned cesarean section are eligible. Patients must understand that
they will not be able to become pregnant naturally in the future
Exclusion Criteria:
• Individuals with a history of any prior cancer who have received chemotherapy within
the past 30 days or radiotherapy to abdomen or pelvis at any prior time
• Prior history of ovarian cancer, including low malignant potential neoplasms (LMP),
primary peritoneal carcinoma, or fallopian tube carcinoma
• Patients medically unfit for the planned surgical procedure
• Patients with abnormal screening tests (TVUS, CA-125) suspicious for occult or gross
pelvic malignancy or neoplasm within the past 180 days
• An abnormal TVUS is defined as morphologic or structural variations suspicious
for ovarian malignancy or complex cystic lesions (simple cysts < 5 cm in maximal
diameter are not exclusionary)
• An abnormal CA-125 is defined as a level > 50 U/ml in premenopausal individuals
if they are not current users of oral contraceptives; an abnormal CA-125 is
defined as a level > 40 U/ml for premenopausal individuals who are current users
of oral contraceptives. An abnormal CA-125 is defined as a level > 35 U/ml in
postmenopausal individuals.
Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer
The purpose of this research is to determine the expression of prostate specific membrane
antigen (PSMA) in human epidermal growth factor receptor 2 (HER2)-negative, androgen receptor
(AR)-positive metastatic breast cancer, and to determine its role in resistance to the
anti-androgen, bicalutamide. The investigators hypothesize that PSMA expression will
correlate with resistance to anti-androgen therapies, as has been documented in prostate
cancer, and this can be used to select patients most likely to benefit from these therapies
in future clinical trials. 15 people with HER2-negative, AR-positive metastatic breast cancer
will be enrolled and be on study for about 3 days.
Steve Cho
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04573231
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients diagnosed with metastatic HER2-negative breast cancer AR expression of ≥ 10%
Exclusion Criteria:
• Other (non-breast) known active malignancy. Participants with previously treated
cancers which are in remission or have no evidence of disease are eligible.
• Unable to lie flat during or tolerate PET/CT
• Participants with any medical condition or other circumstances that, in the opinion of
the investigator, compromise the safety or compliance of the subject to produce
reliable data or completing the study
• Women of childbearing potential must not be pregnant or breast feeding (pregnancy test
negative within 7 days prior to PET/CT
Breast Cancer, HER2-negative Breast Cancer, Metastatic Breast Cancer, Breast
A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
The primary purpose of this study is to determine the antitumor activity of enfortumab
vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1.
This study will also assess other measures of antitumor activity; overall survival (OS); as
well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab
vedotin + pembrolizumab in cohort 9.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04225117
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Subject is considered an adult according to local regulation at the time of signing
the informed consent form (ICF).
• Subject has measurable disease by RECIST Version 1.1.
• Subject has accessible archival tumor tissue from either the primary tumor or a
metastatic site, for which source and availability have been confirmed prior to study
treatment. If no archival tumor tissue is available, the subject will have a biopsy to
obtain tumor tissue prior to study treatment. If the subject is unable to undergo a
biopsy due to safety concerns, enrollment into the study must be discussed with the
medical monitor.
• For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for
programmed cell death-ligand 1 (PD-L1) central testing during screening if no local
PD-L1 test result is available. Central test result for PD-L1 will be required prior
to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming
CPS ≥ 1, archival or fresh tissue sample for exploratory analysis should be submitted
within 5 days of enrollment.
• Subject has ECOG performance status of 0 or 1.
• Subject has the following baseline laboratory data. If a subject has received a recent
blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood
transfusion.
• absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• platelet count ≥ 100 × 10^9/L
• hemoglobin ≥ 9 g/dL
• serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
subjects with Gilbert's disease
• creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards
or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can
also be used instead of CrCl).
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Subject agrees not to participate in another interventional study while receiving
study treatment in the present study.
• Additional contraceptive requirements exist for male and female subjects.
Disease Specific
Inclusion Criteria:
• Evidence of progression on or after the last regimen received.
• Locally advanced or metastatic disease that is not amenable to curative intent
treatment.
Cohort 1: HR+/HER2- breast cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor
[ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast
cancers and are not considered a candidate for further hormonal therapy. Subject will
be considered HR+ if biopsies show ≥ 1% expression of ER or PR as per current American
Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. No limit applies to
endocrine therapies. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a
line of cytotoxic therapy.
• Subject has progressed, relapsed, or discontinued for toxicity during or after
receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent
kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required.
Cohort 2: triple negative breast cancer (TNBC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal
TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1%
expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either
0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not
amplified) as per current ASCO/CAP guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. Poly(ADP-ribose)
polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
• Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1)
or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or
PD-L1 expression and local treatment guidelines and has progressed or discontinued
treatment due to toxicity, or therapy is contraindicated for subject.
Cohort 3: squamous non-small cell lung cancer (NSCLC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically or cytologically-confirmed squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma
kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations
are eligible if treated with mutation targeted therapy and have progressed,
relapsed, or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression had occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 4: non-squamous non-small cell lung cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed non-squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are
eligible if treated with mutation targeted therapy and have progressed, relapsed,
or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression has occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 5: second-line or later head and neck cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed head and neck cancer.
• Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors
and/or parotid gland tumors are not eligible for Cohort 5.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months after completion.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohorts 6, 7 and 8: gastric or gastroesophageal junction (GEJ) or esophageal adenocarcinoma
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal
cancer.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if
relapsed or progressed ≤ 6 months after completion.
• Subject must have received a HER2 directed therapy if known to have HER2 positive
cancer.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 9: 1L HNSCC
• Subject has histologically- or cytologically-confirmed head and neck squamous cell
carcinoma.
a. Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or
parotid gland tumors are not eligible for Cohort 9.
• Subject has recurrent or metastatic disease that is incurable by local therapies.
• Subject's tumor sample has PD-L1 combined positive score (CPS) of ≥ 1 as determined by
local or central IHC testing.
• Subject has had no prior systemic therapy administered with the exception of systemic
therapy completed > 6 months prior if given as part of multimodal treatment for
locally advanced disease. Subjects who have received a PD-1 or PD-L1 inhibitor in the
curative setting are eligible if it has been at least 12 months since last dose of the
anti PD-L1 agent.
• Subject has ANC ≥ 1.5 × 10^9/L.
• International normalized ratio (INR) OR prothrombin time (PT) and activated partial
thromboplastin (aPTT) both ≤ 1.5 × ULN unless subject is receiving anticoagulant
therapy as long as PT or aPTT is within the therapeutic range of intended use of
anticoagulants. PTT may be used if local lab is unable to perform aPTT.
• For subjects with oropharynx tumors, subject has results from testing of HPV status by
p16 testing.
Exclusion Criteria:
For All Cohorts:
• Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
• Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
metastases are permitted on study if all the following are true:
• CNS metastases have been clinically stable for ≥ 6 weeks prior to screening
• If requiring steroid treatment for CNS metastases, the subject is on a stable
dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks
• Baseline imaging scans show no evidence of new or enlarged brain metastasis
• Subject does not have leptomeningeal disease
• Subject has ongoing clinically significant toxicity (Grade 2 or higher with the
exception of alopecia) associated with prior treatment (including systemic therapy,
radiotherapy or surgery).
• Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or
panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis,
uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs
requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), are
excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or
panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of
hormone replacement therapy (if indicated).
• Subject has a history of uncontrolled diabetes mellitus within 3 months before the
first dose of study treatment. Uncontrolled diabetes (within 3 months before first
dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with
associated diabetes symptoms (polyuria or polydipsia) that are not otherwise
explained. The lowest HbA1c during the screening period will be used to determine
eligibility.
• Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E
(MMAE) based antibody-drug conjugates (ADCs).
• Subject has a second malignancy diagnosed within 3 years before first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy.
Subjects with non-melanoma skin cancer, localized prostate cancer treated with
curative intent with no evidence of progression, low-risk or very low-risk (per
standard guidelines) localized prostate cancer under active surveillance/watchful
waiting without intent to treat, or carcinoma in situ of any type (if complete
resection was performed) are allowed.
• Subject is currently receiving systemic antimicrobial treatment for viral, bacterial,
or fungal infection at the time of first dose of study treatment. Routine
antimicrobial prophylaxis is permitted.
• Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg]
reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is
detected).
• Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or
2).
• Subject has documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction or cardiac symptoms
(including congestive heart failure) consistent with New York Heart Association Class
III-IV within 6 months prior to the first dose of study drug.
• Subject has major surgery within 4 weeks prior to first dose of study drug.
• Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or
antitumor treatment with immunotherapy that is not completed 2 weeks prior to first
dose of study drug.
• Subject has known hypersensitivity to enfortumab vedotin or to any excipient contained
in the drug formulation of enfortumab vedotin (including histidine, trehalose
dihydrate and polysorbate 20) OR subject has known hypersensitivity to
biopharmaceutical produced in Chinese hamster ovary cells.
• Subject has known active keratitis or corneal ulcerations. Subject with superficial
punctate keratitis is allowed if the disorder is being adequately treated.
• Subject has any condition which makes the subject unsuitable for study participation.
Cohort 9: 1L HNSCC
• Had PD within 6 months of completion of curatively intended systemic treatment for
locoregionally advanced HNSCC.
• Has had an allogeneic tissue/solid organ transplant. Has severe hypersensitivity
(≥grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that
required steroids or has current pneumonitis / interstitial lung disease.
• Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease
(e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating
investigator.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
1. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed.
2. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered
standard of care.
3. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or
resolved childhood asthma/atopy will not be excluded.
4. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or
local steroid injections will not be excluded.
5. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's
syndrome will not be excluded.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent in the
recurrent/metastatic setting. If anti-PD-1 or anti-PD-L1 agent was given as part of
curative intent therapy, it must be at least 1 year since last dose.
• Has received a live vaccine within 30 days of planned start of study therapy. Examples
of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette
Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally
killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,
FluMist®) are live attenuated vaccines and are not allowed.
• Subject has active tuberculosis
Locally Advanced or Metastatic Malignant Solid Tumors, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Larynx, Lung, Breast, Eye and Orbit, Head and Neck, Melanoma/Skin cancer
A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer
This phase I trial studies the side effects and best dose of peposertib when given together
with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low
grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving peposertib and pegylated
liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer
compared to pegylated liposomal doxorubicin hydrochloride alone.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04092270
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian,
fallopian tube or primary peritoneal cancer are eligible. This includes, but is not
limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/
high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not
otherwise specified
• NOTE: Patients who have evidence of DDR deficiency /HRD are eligible if they are
at the point in their disease course where they are appropriate candidates for
single agent Doxil
• EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low
grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)
• Patients accrued to the LGSOC cohort will have recurrent or persistent low grade
serous ovarian cancer or grade 1 serous ovarian cancer
• Patients accrued to the HGSOC cohort will have recurrent or persistent high grade
serous ovarian cancer
• Patients must have measurable disease by defined Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria
• Prior therapy:
• Patients must have received at least one prior line of platinum-based
chemotherapy
• Patients can have received an unlimited number of additional lines of
chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
• Any prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted therapy, immunotherapy, or hormonal therapy must be
discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest)
prior to study treatment initiation
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in
patients < 18 years of age, children are excluded from this study, but will be
eligible for future pediatric trials
• Patients with platinum-sensitive ovarian cancer are eligible for only the dose
expansion phase if their provider feels that PLD would be an appropriate treatment
option for them. Patients with platinum-sensitive ovarian cancer should also be
offered any higher priority studies for which they are potentially eligible and/or
platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients must have a cardiac ejection fraction >= the institutional lower limit of
normal (LLN)
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
• Alkaline phosphatase =< 2.5 x institutional ULN
• Creatinine clearance > 30 ml/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression. The
patient must be off steroids and clinically stable
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
• The effects of peposertib (M3814) and liposomal doxorubicin on the developing
human fetus are unknown and there is the potential for teratogenic or
abortifacient effects. For this reason, women and men of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study treatment,
and for 6 months after completion of peposertib (M3814) administration. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with peposertib (M3814),
breastfeeding should be discontinued if the mother is treated with peposertib
(M3814)
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
• Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36
months prior to registration must be available for submission for deoxyribonucleic
acid (DNA)/ribonucleic acid (RNA) analysis
Exclusion Criteria:
• Patients are excluded from the dose-escalation phase of the study if they are eligible
for any available therapies known to confer clinical benefit
• Inability to swallow and/or absorb oral medication (patients with a drainage peg are
ineligible)
• Patients may not have received prior anthracyclines (doxorubicin or pegylated
liposomal doxorubicin) for treatment of their ovarian cancer
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia, thyroid
dysfunction, or neuropathy
• Patients who are receiving any other investigational agents within 28 days prior to
start of treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to peposertib (M3814) or pegylated liposomal doxorubicin
• Patients who cannot discontinue concomitant medications or herbal supplements that
potentially interact with peposertib (M3814)
• The following categories of medications and herbal supplements must be
discontinued prior to starting study treatment:
• Strong inducers/inhibitors of CYP3A4/5, CYP2C9, and CYP2C19
• Substrates of CYP3A4/5, CYP1A2, and CYP2B6 with a narrow therapeutic index
• Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6 and substrates of
P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 with a narrow therapeutic index. Close
monitoring is advised
• Because the lists of these agents are constantly changing, it is important to
regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk
of interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or
herbal product. Patient Drug Interactions Handout and Wallet Card) should be
provided to patients
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients
may confer with the study doctor to determine if such medications can be discontinued.
These must be discontinued >= 5 days prior to study treatment. Patients do not need to
discontinue calcium carbonate
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
are excluded
• Patients who have received a live attenuated vaccine within 30 days of dosing with
peposertib (M3814)
• Patients with uncontrolled intercurrent illness, including but not limited to ongoing
or active infection
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because peposertib (M3814) is DNA-PK
inhibitor agent with the potential for teratogenic or abortifacient effects. Because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with peposertib (M3814), breastfeeding should be
discontinued if the mother is treated with peposertib (M3814). These potential risks
may also apply to other agents used in this study
• Patients with significant (uncontrolled) cardiac conduction abnormalities are excluded
Making Informed Choices on Incorporating Chemoprevention Into Care (MiCHOICE)
This trial studies the implementation of web-based decision support tools for patients with
atypical hyperplasia or lobular carcinoma in situ and healthcare providers. Decision support
tools are designed to improve informed choice about breast cancer chemoprevention.
Recognizing barriers and facilitators that can influence the adoption of decision support
tools at recruitment centers may help researchers learn how to best implement them into
clinical practice.
Kari Wisinski, MD
All
Not specified
N/A
This study is also accepting healthy volunteers
NCT04496739
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must have histologically-confirmed atypical hyperplasia (AH) or lobular
carcinoma in situ (LCIS) documented by breast pathology report at any time in the
past. Patients with borderline breast lesions and pleomorphic LCIS are also eligible
• Patients must be women at least 35 and no more than 74 years of age at registration,
since the Breast Cancer Surveillance Consortium (BCSC) risk calculator is valid only
for this age range
• Both pre/perimenopausal and postmenopausal women are eligible
• Patients must be able to read and write in English or Spanish since study
questionnaires and educational materials are only available in English and Spanish
• Baseline questionnaires must be completed prior to patient registration
• The S1904 Patient Contact form must be completed prior to patient registration
• Patients must be able to access the internet and receive email or text messages. This
is required to access study materials and receive email/text message reminders from
the S1904 Study Team at Columbia University Irving Medical Center (CUIMC). The patient
decision aid, RealRisks, is accessible via smartphones, tablets, or personal
computers. If patients do not own these devices, local study personnel will provide
resources for patients to access RealRisks via computer kiosks or tablets in clinic
waiting rooms or public locations, such as community centers or public libraries
• Patients and healthcare providers must be informed of the investigational nature of
this study and must sign and give written informed consent in accordance with
institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
• IMPLEMENTATION: Providers who enrolled in S1904 at Group 2 (intervention) recruitment
center and consented to future contact are eligible to participate in the interviews
• IMPLEMENTATION EVALUATION: Patients who registered to S1904 at a Group 2
(Intervention) Recruitment Center and consented to be contacted for future research
are eligible to participate in the interviews
• Recruitment Centers must be National Clinical Trials Network (NCTN), National Cancer
Institute Community Oncology Research Program (NCORP) or Minority Underserved
(MU)-NCORP institutions
• Recruitment Centers must have an active EHR and patient portal used in the outpatient
clinics which is common and accessible across all sites belonging to the Recruitment
Center
• Recruitment Centers must be willing to allow the S1904 study team access to the site's
application program interface (API) for integration of the study materials (standard
educational materials and decision support tools) into the EHR and patient portal.
(NOTE: Both Group 1 (control) and Group 2 (intervention) recruitment centers may
access the standard educational materials via the patient portal or uniform resource
locator (URL)/website)
• Recruitment centers must see at least 50 AH and/or LCIS patients per year
• Recruitment centers must identify a lead principal investigator (PI) to facilitate
recruitment and retention of patients and healthcare providers and to participate in
quarterly stakeholder meetings/conference calls
• Recruitment centers must be willing to register at about 16 patients and 5 healthcare
providers to the study
• Recruitment Centers must be willing to submit monthly screening logs to CUIMC
• Providers must regularly see patients with AH or LCIS at an approved recruitment
center
• Providers must be willing to provide informed consent and complete an online baseline
questionnaire
• Providers who will register patients must be registered members of a Cooperative Group
• Providers who register patients to S1904 must be willing to see those same patients
for their 6-month study visits, as the provider intervention tools require that the
"treating investigator" as designated in OPEN and the provider at the 6-month study
visit be the same
Exclusion Criteria:
• Patients must not have a history of invasive breast cancer or ductal carcinoma in situ
• Patients must not have prior or current use of selective estrogen receptor modulators
(SERMs) or aromatase inhibitors (AIs)
• NOTE: The following are approved SERMS and AIs, however, the study is not limited
to these.
• SERMs: tamoxifen, raloxifene
• AIs: anastrozole, exemestane, letrozole
• Patients must not be currently taking hormone replacement therapy
• Patients must not have a history of bilateral mastectomies or breast implants since
the risk calculator is not applicable to these women
• Patients must not be pregnant or lactating
• Premenopausal patients must not have a history of thromboembolism, since it is a
contraindication to tamoxifen. Tamoxifen is the only Food and Drug Administration
(FDA)-approved drug for breast cancer chemoprevention among high-risk premenopausal
women, whereas postmenopausal women are eligible for both SERMs and AIs
Atypical Hyperplasia of the Breast, Lobular Breast Carcinoma In Situ, Pleomorphic Lobular Breast Carcinoma In Situ, Breast
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer (DARE)
A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for
high Residual risk, stage II-III, Estrogen Receptor positive, HER-2 negative breast cancer
(DARE)
Mark Burkard, MD, PhD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT04567420
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
•4.1.1. Stage II or III, HER2 negative, ER positive invasive breast cancer in male or
female patients. For this study, ER positivity is defined as equal to or greater than 10%
ER positivity by immunohistochemistry, regardless of progesterone receptor (PR) status.
Patients with PR positive but ER negative cancer are not eligible. HER2 negative status is
defined as per the ASCO/CAP 2018 practice guidelines.
(i) if patients have synchronous bilateral ER+ breast cancer tissue from both sites should
be submitted to Natera to perform ctDNA testing.
(ii) patients with multifocal/multicentric tumors are eligible and the largest focus of
cancer should be submitted for testing. All tumors must meet pathological criteria for
HER2-and ER+ status.
(iii) For. patients who received neoadjuvant therapy and have discordant ER and HER2
results between the diagnostic biopsy (pre-treatment) and surgical pathology (post
neoadjuvant therapy), the ER+ and HER2- status of the post-treatment specimen determine
eligibility.
4.1.2. Currently taking an aromatase inhibitor, or tamoxifen, as adjuvant endocrine therapy
and have completed at least 6 months (i.e. 24 weeks), but no more than 7 years with 3 more
years planned, of endocrine therapy. Patients may register for the screening phase of the
study within the first 6 months of adjuvant endocrine therapy but the first ctDNA testing
must occur at, or after, 6 months of endocrine therapy.
(i) Adjuvant bisphosphonate therapy is allowed. (ii) LHRH analogues are required for
premenopausal patients randomized to receive fulvestrant.
4.1.3. Clinical and pathological high risk for recurrence defined as any one of the
following: (i) At least a 15% predicted risk of death within 10 years using ePREDICT V2.1
(https://breast.predict.nhs.uk/tool), or (ii) At least 15% or greater risk of distant
metastasis within 10 years using RSPC,
(https://tools.genomichealth.com/Tools/RSPCTool.aspx), or (iii) At least 15% or greater
risk of distant metastasis within 10 years CTS5 (https://www.cts5-calculator.com) for
patients who have completed a minimum of 4 years of adjuvant endocrine therapy, or (iv)
Tumor size > 5 cm, regardless of lymph node status, or (v) 1-3 involved axillary lymph
nodes and at least one of the following;
• Tumor size > 3 cm,
• High histological grade (e.g. grade 3).
• High genomic risk defined as Oncotype Dx Recurrence Score >26, EndoPredict score >4,
Prosigna risk of recurrence score ≥ 60, or Mammaprint high risk.
(vi) Patients who have received pre-operative (neoadjuvant) chemotherapy must have either:
• greater than or equal to 3 cm invasive residual cancer regardless of nodal status AND
grade 3 disease or RS>26/MammPrint High/Prosigna high/Endopredict high status, or
• greater than or equal to 1 cm invasive residual cancer (ypT1c) and at least 1 positive
lymph node (ypN+) AND grade 3 disease, or RS>26, or MammPrint High, or Endopredict
high or Prosigna high status.
4.1.4. Patients must have FFPE tissue from the primary tumor available for submission to
Natera to perform ctDNA assay (see Appendix B for tissue submission instructions).
4.1.5. Signed and dated informed consent, including willingness to be randomized to
standard of care versus fulvestrant + palbociclib.
4.2 Inclusion and exclusion criteria for treatment randomization
Inclusion criteria for randomization
4.2.1. ctDNA positivity by the Signatera assay, defined as 2 of the 16 cancer specific
markers positive in plasma.
4.2.2. Patients with positive Signatera results obtained in the context of commercial
testing, outside of the screening phase of this trial, are also eligible for randomization
if they meet other eligibility criteria.
4.2.3. No evidence of metastatic disease on CT scan of the chest, abdomen and pelvis.
• If imaging, after review with a radiologist, is low probability for metastatic
disease, patients may proceed to randomization.
• Patients with suspicious but inconclusive imaging results should undergo a diagnostic
biopsy, if biopsy is negative patients are eligible for randomization.
• Patients with positive imaging that is conclusive of metastatic disease, or with
biopsy proven metastatic disease, are not eligible for randomization.
4.2.4. Pre-menopausal women and male patients must be willing to use an adequate method of
contraception for the duration of trial treatment and for 4 additional weeks after
completion of treatment in the control arm, and for 2 years after the last dose of
fulvestrant, if randomized into the experimental arm.
Post-menopausal status is defined as:
• Documented bilateral oophorectomy.
• Age ≥ 60 years.
• Age < 60 years and amenorrhoeic for ≥ 12 consecutive months and FSH and estradiol
levels in the post-menopausal range according to the institutional reference range for
post-menopausal.
Adequate contraception is defined as ONE highly effective form (i.e. abstinence, surgical
sterilization through bilateral tubal ligation, vasectomy), or TWO effective forms (e.g.
non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream /
suppository).
•Abstinence is to be interpreted as "true abstinence" for heterosexual intercourse and
therefore, "periodic abstinence" (e.g. calendar, symptothermal, post-ovulation methods) and
withdrawal (coitus interruptus) are not considered highly effective.
Exclusion Criteria
4.1.5. Prior or current treatment with fulvestrant, or current treatment with a CDK4/6
inhibitor, or treatment in the prior 12 months, or participants in the PENELOPE and PALLAS
clinical trials.
4.1.6. Patients cannot start participation in another therapeutic clinical trial for breast
cancer after enrollment in this trial.
4.1.7. Patients with current or past invasive cancer, other than breast cancer are not
eligible, except:
• Adequately treated basal or squamous cell carcinoma of the skin are eligible.
• Cancer survivors of previously diagnosed invasive cancer, who were treated with a
curative intent, have no evidence of disease recurrence for 5 years or more, and are
considered low risk for future recurrence by the treating physician are also eligible.
4.1.8. Patients with a second HER2 positive or triple negative synchronous breast cancer
are not eligible.
Exclusion criteria for randomization
4.2.5. Patients with known contraindications to receive fulvestrant and palbociclib or
those who are unable to tolerate these drugs are not eligible.
• Absolute neutrophil count less than <1000/mm3;
4.2.6. Any concurrent severe and uncontrolled medical condition that would, in the
Investigator' opinion cause unacceptable safety risks or compromise compliance with the
protocol including but not limited to:
• Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral medication (e.g. Crohn's disease, ulcerative diseases,
uncontrolled chronic nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).
• History of pneumonitis, interstitial lung disease or pulmonary fibrosis.
• Known history of Human Immunodeficiency Virus (HIV) (testing is not mandatory).
• Known active Hepatitis B or Hepatitis C (testing is not mandatory).
• Females who are pregnant or breastfeeding.
• History of bleeding diathesis (i.e. disseminated intravascular coagulation, clotting
factor deficiency) that preclude the IM injections of fulvestrant or LHRH agonist as
applicable.
4.2.7 Patients taking any CYPC3A4 strong inducers and inhibitors, that cannot be changed.
Additional Support Program Via Text Messaging and Telephone-Based Counseling for Breast Cancer Patients Receiving Hormonal Therapy
This phase III trial compares an additional support program (text message reminders and/or
telephone-based counseling) with usual care in making sure breast cancer patients take their
endocrine therapy medication as prescribed (medication adherence). Medication adherence is
how well patients take the medication as prescribed by their doctors, and good medical
adherence is when patients take medications correctly. Poor medication adherence has been
shown to be a serious barrier to effective treatment for hormone receptor positive breast
cancer patients. Adding text message reminders and/or telephone-based counseling to usual
care may increase the number of days that patients take their endocrine therapy medication as
prescribed.
Toby Campbell, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04379570
Show full eligibility criteria
Hide eligibility criteria
• Women with an initial pathologically confirmed diagnosis of stage I-III, hormone
receptor positive, HER2-neu negative, invasive breast cancer within 18 months prior to
enrollment
• Women who have undergone neo-adjuvant chemotherapy who have no residual invasive
disease post-surgery are eligible based on an initial pathologically confirmed
diagnosis
• Hormone receptor positive is defined as estrogen receptor (ER) and/or
progesterone receptor (PR) of > 1%
• HER2-neu negative is defined as 0-1+ by immunohistochemical (IHC) analysis, or
non-amplified by fluorescence in situ hybridization (FISH) analysis
• Patients must have received cancer-directed surgery, and/or completed all other
adjuvant therapy, except reconstruction
• Patients must have initiated an endocrine therapy drug within the 6 months prior to
registration, OR have received a prescription with stated intent to initiate within 6
weeks after registration
• No history of previous cancer as follows:
• Invasive or non-invasive breast cancer at any time
• Non-breast cancer, within the past 5 years, excluding non-melanoma skin cancer
• Patients must be willing to use a smart phone for study activities
• Patient is NOT to be deemed ineligible during the recruitment process if they do
not have a smart phone
• If a participant does not own a smart phone or has limited data or texting
capabilities or their smart phone cannot support the Alliance electronic patient
reported outcomes (ePRO) survey application (app), a smart phone and service can
be provided to the participant at no cost through the Ohio State University (OSU)
partnership with Verizon Wireless for the duration of the study activities
• The CRP is ONLY to discuss this option with those patients who self-identify a
phone-related barrier to participation, including: lack of a smart phone,
insufficient phone plan (minutes/text/data), or a smart phone incompatible with
the Alliance ePRO app
• For OSU -provided phones, charges will be paid by the grant through the
intervention period. At the end of the 12-month intervention period, patients
will be responsible for paying monthly fees, if continued service is desired. The
physical phones will belong to the patients at the end of their study activities
• Patients must be willing to use a Pillsy medication event monitoring system for the
duration of study participation
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and read English
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2 Negative Breast Carcinoma, Hormone Receptor Positive Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Breast
Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors
This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety,
tolerability, MTD PK, and PD of TJ033721 in subjects with advanced or metastatic solid
tumors.
Jeremy Kratz, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04900818
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Subjects with advanced or metastatic solid tumor in subjects whose disease has
progressed despite standard therapy, or who has no further standard therapy, or who is
unsuitable for available standard treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate
organ function
• Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding
combined positive score (CPS)
For dose expansion study only:
• Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, and
esophageal adenocarcinoma without further standard therapy or unsuitable for available
standard treatment options.
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay
Exclusion Criteria
• Prior exposure to CLDN18.2 -targeted therapy
• Prior exposure to 4-1BB agonists
• Second malignancy within the last 3 years with the exception of cutaneous squamous
cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ
• Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
• Unstable/active ulcer or digestive tract bleeding within 6 weeks
• Active autoimmune disease requiring systemic treatment within the past 2 years
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or
pneumonitis requiring treatment
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are clinically stable and
without requirement of steroid treatment for at least 14 days prior to first dose of
study treatment;
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure,
severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart
failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism,
pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein
thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months
• Diagnosis of immunodeficiency such as known active HIV
• Any active infection requiring parenteral treatment
Solid Tumor, Advanced Cancer, Metastatic Cancer, Gastric Cancer, Gastroesophageal Junction Carcinoma, Esophageal Adenocarcinoma, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
T-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in
preventing breast cancer from coming back (relapsing) in patients with high risk, HER2
positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a
chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches
to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors,
and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some
of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in
preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared
to T-DM1 alone.
Kari Wisinski, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04457596
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• HER2-positive status will be based on pretreatment biopsy material and defined as an
immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH)
according to current American Society of Clinical Oncology (ASCO) College of American
Pathologists (CAP) guidelines. Central testing is not required
* Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on
pretreatment biopsy material). Hormone receptor positive status can be determined by
either known positive estrogen receptor (ER) or known positive progesterone receptor
(PR) status; hormone receptor negative status must be determined by both known
negative ER and known negative PR
• Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive
disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0
tumors are not eligible at initial breast cancer diagnosis are not eligible)
• Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or
lymph nodes per the surgical pathology report are eligible; however, patients with HR+
HER2+ cancers must have node-positive residual disease per the surgical pathology
report in order to qualify for the study. The presence of residual invasive disease in
the breast is not mandatory for these patients
• Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core
biopsy) are eligible even if they have node-negative disease per the surgical
pathology report
• The residual disease tissue (breast and/or lymph nodes) is not required to be
HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2
status at the time of the initial breast cancer diagnosis
* Note: The presence of micrometastases in lymph nodes after preoperative therapy
counts as residual disease, whereas the presence of isolated tumor cells does not
• Patients with synchronous bilateral invasive disease are eligible provided both
lesions were confirmed to be HER2-positive, and at least one of the lesions meets the
criteria outlined above. Multifocal disease is allowed, as long as the largest
biopsied breast tumor was HER2-positive
• Patients must have received neoadjuvant chemotherapy with one of the following
regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin
(TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P));
docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P));
fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab
(FAC-TH(P)), or
fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)).
Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is
acceptable
• Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.
• Prior treatment must have consisted of >= 6 cycles of chemotherapy and
HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9
weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food
and Drug Administration [FDA]-approved biosimilars). Patients who have received
at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also
eligible if they received >= 6 cycles of systemic therapy prior to enrollment.
Note: Patients who complete at least nine of a planned twelve doses of weekly
paclitaxel, or three of a planned four doses of docetaxel, but discontinue
prematurely due to toxicity are eligible. Patients receiving dose-dense
chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane)
instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous
trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is
also allowed.
• Patients who received neoadjuvant systemic therapy which included experimental
HER2-targeted therapy/therapies are potentially eligible, as long as the
investigational agent was not a HER2-targeted antibody-drug conjugate (e.g.
T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase
inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
• Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These
patients will be randomized to receive a further 14 cycles of T-DM1 and
tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been
administered =< 5 weeks prior to registration
* Note: Both of the following two criteria need to be met for the patient to be
eligible for this study
• An interval of no more than 12 weeks between the completion date of the last
definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither
given, breast surgical date) and the date of registration. Concurrent radiation
therapy is permitted while receiving study treatment
• Patients must be registered on study within =< 180 days of the date of the most
recent definitive breast cancer surgery (not including reconstructive surgery)
• All systemic chemotherapy should have been completed preoperatively unless
participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG
DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design,
drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP
off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet
eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to
surgery immediately after the de-escalated trial regimen must receive postoperative
chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to
enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles
post-operatively). The postoperative chemotherapy regimen prescribed is at the
discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation
of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy
(while awaiting a surgical date or an official pathology report) is allowed for all
study participants
• Toxicities related to prior systemic treatment should have resolved or be at baseline,
apart from alopecia and peripheral neuropathy =< grade 1
• Adequate excision: surgical removal of all clinically evident disease in the breast
and lymph nodes as follows:
• Breast surgery: total mastectomy with no gross residual disease at the margin of
resection, or breast-conserving surgery with histologically negative margins of
excision
• For patients who undergo breast-conserving surgery, the margins of the resected
specimen must be histologically free of invasive tumor and ductal carcinoma in
situ (DCIS) as determined by the local pathologist. If pathologic examination
demonstrates tumor at the line of resection, additional operative procedures may
be performed to obtain clear margins. If tumor is still present at the resected
margin after re-excision(s), the patient must undergo total mastectomy to be
eligible. Patients with margins positive for classic lobular carcinoma in situ
(LCIS) are eligible without additional resection
• Lymph node surgery ** The axilla needs to be evaluated with either sentinel node
biopsy or axillary lymph node dissection. If patients have a sentinel lymph node
biopsy and sentinel nodes are negative, no further axillary treatment is
necessary. If patients have isolated tumor cells (ITCs) in the setting of
residual breast disease, at least one of the following is required: axillary
lymph node dissection (ALND) or planned nodal irradiation. If patients have
micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are
required. Of note, co-enrollment on Alliance A011202 is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted
to achieve eligibility)
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the
institutional normal range for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal (ULN)
• Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or
multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no
decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy
LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55%
after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated
once up to 3 weeks following the initial screening assessment to assess eligibility
Exclusion Criteria:
• No adjuvant treatment with any anti-cancer investigational drug within 28 days prior
to registration
• Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing
potential only, a negative serum pregnancy test done =< 7 days prior to registration
is required
• Patients with known active and/or untreated hepatitis B or hepatitis C or chronic
liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has
been treated and cleared and normal liver function are eligible to participate in the
study if the other eligibility parameters are met
• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of
registration
• Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the
surgical pathology report
• Evidence of recurrent disease following preoperative therapy and surgery
• Patients for whom radiotherapy would be recommended for breast cancer treatment but
for whom it is contraindicated because of medical reasons (e.g., connective tissue
disorder or prior ipsilateral breast radiation)
• History of exposure to the following cumulative doses of anthracyclines: doxorubicin >
240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2.
For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3
symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA)
criteria class >= II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not
controlled by adequate medication, severe conduction abnormality, or clinically
significant valvular disease
• High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate >
100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or
higher-grade atrioventricular block (AV)-block (second degree AV-block type 2
[Mobitz 2] or third degree AV-block)
• Significant symptoms (grade >= 2) relating to left ventricular dysfunction,
cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative
therapy
• History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with
prior trastuzumab treatment (e.g., during preoperative therapy)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic
blood pressure > 100 mmHg)
• Current severe, uncontrolled systemic disease
• Major surgical procedure unrelated to breast cancer or significant traumatic injury
within 28 days prior to registration or anticipation of the need for major surgery
during the course of study treatment
• History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity
to trastuzumab or murine proteins or any components of the product
• Peripheral neuropathy of any etiology that exceeds grade 1
• Assessment by the investigator as being unable or unwilling to comply with the
requirements of the protocol
• Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4
or CYP2C8 inducer within 5 days prior to registration is prohibited.
• Please note that use of sensitive CYP3A substrates should be avoided two weeks
before registration and during study treatment. Additionally, CYP3A4 or CYP2C8
inducers are prohibited as concomitant medications within 5 days following
discontinuation of tucatinib treatment. Patients who require medications that are
known to be sensitive substrates of CYP3A4 with a narrow therapeutic window
should be excluded.
Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, HER2 Positive Breast Carcinoma, Invasive Breast Carcinoma, Multifocal Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8, Synchronous Bilateral Breast Carcinoma, Breast
Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)
The purpose of this study is to find out whether the study drug, LY3537982, is safe and
effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must
have already received or were not able to tolerate the standard of care, except for specific
groups who have not had cancer treatment. The study will last up to approximately 4 years.
Dustin Deming, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04956640
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors
version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or
circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally
advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any
significant ongoing adverse events (AEs), (except in certain scenarios).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, (i.e., one of the two arms with LY3537982 in combination
with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab,
pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage
IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic
setting and not suitable for curative intent radical surgery or radiation therapy.
Previously untreated patients who received adjuvant and neoadjuvant therapy are
eligible if the last dose of the systemic treatment was completed at least 6 months
prior to enrollment. For untreated patients in the arm with LY3537982 in combination
with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated
within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in
combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of
any or all of the drugs other than LY3537982 may be initiated within 21 days prior to
enrollment. Start of study treatment may be delayed to allow sufficient time for
recovery from treatment-related toxicity.
• For one part of the study, participants must have received at least one prior
oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.
Exclusion Criteria:
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an
additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or
carcinomatous meningitis. Patients with treated CNS metastases are eligible for this
study if their disease is asymptomatic, radiographically stable for at least 30 days,
and they do not require treatment with steroids in the two-week period prior to study
treatment. This only applies to some parts of the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in
certain scenarios where such prior therapy is allowed as per protocol.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune
treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study
drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial through 180 days after the last dose of study
medication.
• Known allergic reaction against any of the components of the study treatments.
Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Biliary Tract Neoplasms
Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years (ODYSSEY)
This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG,
Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.
The study aims to create detailed images of the organs and tissue of the human body during
x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which
can be given to patients by injection into a blood vessel or by mouth.
In this study researchers want to find out whether so called gadolinium-based contrast agents
(GBCAs) have an effect on body movement and mental skills when given to participants multiple
times within 5 years.
The study plans to enroll about 2076 participants suffering from a condition for which they
are likely to have at least annually a MRI or another imaging examinations. Only adults up to
65 years will be considered to join this study. During the study duration of 5 years
participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and
will visit the study doctor at least 7 times for physical examinations, laboratory
investigations and tests on body movement and mental skills.
Richard Bruce, MD
All
18 Years to 64 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT04373564
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Participant must be neurologically normal, defined as free of unstable neurologic and
psychiatric disease as confirmed by a normal neurologic examination at screening
• Participant (GBCA-exposed or controls) agrees to undergo unenhanced magnetic resonance
imaging (UE-MRI) of the brain at enrollment and at the end of the observation period
(5 years)
• Participants should have at least 1 of the following indications: a) Medium to high
risk for breast cancer or dense breasts undergoing breast cancer screening with MRI,
b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillance
for prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Child
class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for
surveillance of hepatocellular carcinoma development, d) Low-grade colorectal cancer
or neuroendocrine tumor undergoing screening for liver metastases or e) Branch-duct
intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm)
undergoing imaging surveillance.
In addition, for participants in the GBCA Arms only:
• Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations with the
same GBCA at least annually throughout the 5-year study duration
• Prospective participants with up to 3 well documented GBCA administrations prior to
study screening are acceptable, provided that the imaging was performed with the same
GBCA as the one to be prospectively used in the study. If the GBCA used cannot be
identified, he/she cannot be enrolled.
For the Control Arm:
• Participants who never had and are not likely to receive any GBCA injection during the
course of the study
• Each control participant must be willing to undergo UE-MRI of the brain at baseline
and at Year 5. In Years 1 to 4, the control participants will undergo their clinically
indicated UE-MRIs, computed tomography (CT), ultrasound, or X-ray procedures
Exclusion Criteria:
• As evidenced by history or determined in the neurologic exam at screening, concurrent
neurological and/or psychiatric disease (or treatments) that could influence the
results of the study's motor and cognitive tests (e.g. Cerebrovascular disease,
Multiple sclerosis, Neurodegenerative disease, Malignant disease other than listed in
indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychotic disorders or
any prior psychotic episode not otherwise specified •any documented prior history of
chronic schizophrenia, Remittent or current medically confirmed major depressive
disorder or bipolar disorder, History of long-term major depression or bipolar
affective disorder with an active episode in the past 2 to 5 years, Neurodevelopmental
disorders (eg, trisomy 21), Uncontrolled severe migraine, Uncontrolled or controlled
anxiety or depression within 6 months before enrollment, Screening scores of ≤24 on
the MMSE and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS)).
• Prior, planned, or ongoing chemotherapy or brain irradiation
• Use of concomitant medication(s) affecting neuro-cognitive or motor function
• Substance or alcohol abuse as determined by the investigator
• Alcoholic cirrhosis
• Renal disease, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73
m2
• History of environmental/occupational/other exposure to one or more chemicals that may
affect cognitive and/or motor function, including, but not limited to, heavy metals
(arsenic [As], cadmium [Cd], lead [Pb], manganese [Mn], and mercury [Hg]), pesticides,
solvents, or carbon monoxide.
• Clinical indications requiring >1 contrast enhanced magnetic resonance imaging
(CE-MRI) every 6 months
• Pregnant or nursing (lactating) women
• Presence of any metal-containing joint implants/prostheses
In addition, for participants in either of the GBCA Arms only:
•Receipt of a GBCA or generic prior to study entry other than the specific GBCA to be
administered during the course of the study.
For participants in the Control Arm only:
• Participants with any previous exposure to a GBCA.
• Participants with any contraindication to UE-MRI examinations.
Motor Function, Cognitive Function, Contrast Media, Breast
A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
This phase III trial compares the safety and effect of adding vinorelbine to vincristine,
dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk
rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after
treatment or spread to other parts of the body. This study will also examine if adding
maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the
cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in
a class of medications called vinca alkaloids. They work by stopping cancer cells from
growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only
used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and
may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating
agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the
body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are
chemotherapy medications that work in different ways to stop the growth of cancer cells,
either by killing the cells, by stopping them from dividing, or by stopping them from
spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or
for the rest of patient's life.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04994132
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based
upon institutional histopathologic classification are eligible to enroll on the study
based upon stage, group, and age, as below. FOXO1 fusion status must be determined by
week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include
those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as
ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the
2020 World Health Organization (WHO) Classification as ERMS (classic, dense and
botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical
spindle cell ERMS variant and the newly recognized sclerosing RMS variant).
Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in
the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy
based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on
hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow
involvement on H&E, patients with bone marrow involvement detected ONLY by flow
cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in
situ hybridization (FISH), or immunohistochemistry will NOT be considered to have
clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be
performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within
7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must
be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated
with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is
allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor
(i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation
therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are
eligible, provided they are consented to ARST2031 prior to administration of
radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for
non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must
discontinue chemotherapy for non-malignant conditions prior to starting protocol
therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients
must not have received drugs that are moderate to strong CYP3A4 inhibitors and
inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation
Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Soft Tissue, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma
Clinical Trial of Alpelisb and Tucatinib in Patients With PIK3CA-Mutant HER2+ Metastatic Breast Cancer.
Phase IB/II clinical trial of Alpelisb and Tucatinib in patients with PIK3CA-Mutant
HER2-positive metastatic breast cancer.
Marina Sharifi, MD, PhD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05230810
Show full eligibility criteria
Hide eligibility criteria
Criteria:
Inclusion criteria:
1. Women and men ≥ 18 years old are eligible to enroll
2. ECOG performance status 0-1
3. Life expectancy of more than 6 months, in the opinion of the investigator
4. Histologically confirmed diagnosis of HER2+ locally advanced unresectable or
metastatic breast cancer. HER2 positivity is defined by fluorescence in situ
hybridization (FISH) and/or 3+ staining by IHC according to the latest ASCO/CAP
guidelines.
5. Documented presence of activating mutation in PIK3CA in the tumor, based on the
analysis of solid or liquid biopsy by an assay approved for clinical decision makingby
an FDA-approved test (examples include FoundationOne Liquid®; Guardant360®,
Therrascreen® PIK3CA).
6. Known ER and PR status of the tumor defined by IHC according to the latest ASCO/CAP
guidelines
7. Patients with HR-/HER2+ or HR+/HER2+ breast cancer may enroll
8. HR+/HER2+ patients should be men or post-menopausal women; premenopausal women with
HR+/HER2+ breast cancer are eligible if on ovarian suppression, or agreeable to
mandatory ovarian suppression
9. HR+/HER2+ patients should be agreeable to concomitant treatment with fulvestrant per
study protocol. Prior therapy with fulvestrant is allowed.
10. Patients should have received at least two FDA-approved HER2-targeted agents at any
time in the course of their disease. Note: 1 line of therapy containing EGFR or
HER2-tyrosine kinase inhibitors (for example, neratinib, tucatinib, lapatinib,
afatinib, pyrotinib, etc.) in the metastatic setting is allowed
11. Measurable and/or evaluable disease per RECIST 1.1 criteria and/or RANO-BM criteria
(appendix C). Bone only disease is allowed.
12. CNS inclusion criteria:
Based on screening contrast brain MRI, patients must have one of the following:
1. No evidence of brain metastases 2. Untreated brain metastases not needing immediate
local therapy. For patients with untreated CNS lesions > 2.0 cm on screening contrast brain
MRI, discussion with and approval from the medical monitor is required prior to enrollment
3. Previously treated brain metastases
a. Brain metastases previously treated with local therapy may either be stable since
treatment or may have progressed since prior local CNS therapy, provided that there is no
clinical indication for immediate re-treatment with local therapy in the opinion of the
investigator b. Patients treated with CNS local therapy for newly identified lesions found
on contrast brain MRI performed during screening for this study may be eligible to enroll
if all of the following criteria are met: i. Time since WBRT is ≥ 21 days prior to first
dose of treatment, time since surgical resection of CNS metastases is ≥ 14 days prior to
the first dose of study treatment, or time since SRS is ≥ 7 days prior to first dose of
treatment.
ii. Other sites of disease evaluable by RECIST 1.1 or RANO-BM are present c. Relevant
records of any CNS treatment must be available to allow for classification of target and
non-target lesions. 13. Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥ 75,000/mm3
• Hemoglobin ≥ 9.0 mg/dL without red blood cell transfusion ≤ 7 days prior to Cycle 1
Day 1 of therapy
• Total serum bilirubin ≤ 1.5 X upper limit of normal (ULN) except for subjects with
known Gilbert's disease, who may enroll if the conjugated bilirubin is ≤ 1.5 ULN
• AST (SGOT)/ALT (SGPT) ≤2.5 X ULN;
• Serum creatinine Estimated creatinine clearance ≥50 mL/min as calculated by
Cockroft-Gault formula; actual body weight must be used for creatinine clearance
calculations unless BMI > 30 kg/m2 then lean body weight must be used;≤ 1.5 mg/dL
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
≤ 1.5 X ULN unless on medication known to alter INR and aPTT
• Fasting blood glucose ≤140 mg/dL
• HbA1C≤6.4%
• Left ventricular ejection fraction (LVEF) ≥ 50% (as assessed by ECHO or MUGA)
documented within 4 weeks prior to first dose of study treatment
• Serum or urine pregnancy test (for women of childbearing potential, defined as
premenopausal women who are not permanently sterile due to hysterectomy, bilateral
oophorectomy, bilateral tubal ligation, or bilateral tubal occlusion) negative ≤ 7
days of starting treatment 14. Patients with body mass index >25, or FBG 110-140mg/dL,
or HbA1C 5.7 •6.4% should be agreeable for low glycemic diet and lifestyle
modifications, and consulted by nutritionist prior to initiation of the study drugs.
Ability to understand and the willingness to sign a written informed consent and
comply with the study scheduled visits, treatment plans, laboratory tests and other
procedures.
Exclusion criteria:
1. Patients with contraindications to undergo contrast MRI imaging of the brain are
excluded from the study
2. Pregnancy or breast feeding
3. Any systemic anti-cancer therapy (including hormonal therapy or investigational
agents) or surgery in <14 days prior to the first dose of study treatment WBRT in <21
days, SBRT for CNS disease in <7 days, or palliative radiation to extracranial sites
in <14 days prior to the first dose of study treatment5.
4. Based on screening brain MRI, patients must not have any of the following:
1. Any untreated brain lesions > 2.0 cm in size, unless discussed with medical monitor and
approval for enrollment is given 2. Ongoing use of systemic corticosteroids for control of
symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or
equivalent). However, patients on a chronic stable dose of ≤ 2 mg total daily of
dexamethasone (or equivalent) may be eligible with discussion and approval by the medical
monitor 3. Any brain lesion thought to require immediate local therapy, including (but not
limited to) a lesion in an anatomic site where increase in size or possible
treatment-related edema may pose risk to patient (e.g. brain stem lesions). Patients who
undergo local treatment for such lesions identified by screening contrast brain MRI may
still be eligible for the study based on criteria described under CNS inclusion criteria 3b
4. Known or suspected leptomeningeal disease as documented by the investigator 5. Have
poorly controlled (> 1/week) generalized or complex partial seizures, or manifest
neurologic progression due to brain metastases notwithstanding CNS-directed therapy 5. Any
toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the
exception of peripheral neuropathy, which must have resolved to ≤ Grade 2, and alopecia 6.
More than 1 line of therapy containing tucatinib, lapatinib, neratinib, afatinib,
pyrotinib, or other EGFR or HER2 tyrosine kinase inhibitor in the metastatic setting. Note:
receiving the above medications for <30 days is not considered to be a "line of therapy".
Adjuvant treatment with EGFR or HER2 tyrosine kinase inhibitors does not count.
7. Previous treatment with alpelisib or other PI3K, mTOR or AKT inhibitor of more than 30
days duration.
8. An established diagnosis of diabetes mellitus type I, or uncontrolled diabetes mellitus
type II 9. History of acute pancreatitis within 1 year of screening, or a past medical
history of chronic pancreatitis 10. History of severe cutaneous hypersensitivity reactions
(Steven Johnson syndrome, erythema multiforme or toxic epidermal necrolysis) 11. Active
bacterial, fungal or viral infections requiring treatment with IV antibiotic, IV
anti-fungal, or IV anti-viral drugs 12. Known active hepatitis B (HBV) or, active hepatitis
C (HCV) or human immunodeficiency virus (HIV) infections. Note: pretesting is not required.
Patients with history of treated and cured HCV infection may enroll if they have documented
undetectable viral load.
13. Known HIV infection with CD4+ T-cell (CD4+) counts < 350 cells/μL. Note: pretesting is
not required. Patients with known HIV infection and CD4+ T-cell (CD4+) counts ≥ 350
cells/μL may enroll.
14. Inability to swallow pills or any significant gastrointestinal disease which would
preclude the adequate oral absorption of medications 15. Use of prohibited medications
listed in the Appendix D (strong CYP3A4 inducers or inhibitors, and strong CYP2C8 inducers
or inhibitors) within 3 elimination half-lives prior to initiation of study treatments 16.
Myocardial infarction, severe/unstable angina, percutaneous transluminal coronary
angioplasty/stenting (PTCA), or coronary artery bypass graft (CABG) within 6 month of the
first dose of the study treatment 17. Clinically significant cardio-vascular disease, such
as ventricular arrhythmia requiring therapy, uncontrolled hypertension (defined as
persistent systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg
on antihypertensive medications), or any history of symptomatic congestive heart failure
(CHF) 18. Other severe acute or chronic medical or psychiatric conditions or laboratory
abnormalities that may increase the risk associated with study participation or study drug
administration, or may interfere with the interpretation of study results, or in the
judgment of the investigator would make the subject inappropriate for entry into the study.
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.