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
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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
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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.
Oxaliplatin and Liposomal Irinotecan (Plus Trastuzumab for HER2-positive Disease) in Advanced Esophageal and Gastric Adenocarcinoma
This is an open label, phase II, multi-site trial evaluating the efficacy and safety of the
combination of 5-FU, oxaliplatin, nal-IRI, and immunotherapy (plus trastuzumab for
HER2-positive tumors) as first-line therapy for participants with advanced Esophageal and
Gastric Adenocarcinoma (EGA). The investigators hypothesize that this drug combination will
be better tolerated than current first-line chemotherapy combinations for this disease.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04150640
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Inclusion Criteria:
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Histological or cytological confirmed locally advanced or metastatic EGA. Known HER2
status prior to treatment initiation required. Known PDL1 CPS status prior to
treatment initiation.
• Measurable disease according to RECIST v1.1.
• No prior lines of systemic therapy for advanced disease.
• Participants who had received neoadjuvant or adjuvant therapy or definitive
chemoradiation will be allowed to participate if recurrence occurred 6 months or
longer from the completion of all prior treatments.
• Demonstrate adequate organ function as defined below; all screening labs to be
obtained within 14 days prior to registration
• Absolute Neutrophil Count (ANC) ≥1,500 /μl without the use of hematopoietic
growth factors
• Hemoglobin (Hgb) ≥8 g/dL (blood transfusions are permitted for participants with
hemoglobin levels below 8 g/dL)
• Platelets ≥100,000 /μl
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl). CrCl
calculation using the Cockcroft-Gault formula. ≥50 mL/min for participants with
creatinine levels > 1.5 X institutional ULN
• Bilirubin within normal range for the institution (biliary drainage is allowed
for biliary obstruction)
• Aspartate aminotransferase (AST) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
• Alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
metastases
• Albumin >3.0 g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
of intended use of anticoagulants
• Women of childbearing potential should have a negative urine or serum pregnancy test
within 14 days of study registration. NOTE: Women 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
• Women of childbearing potential and males must be willing to abstain from heterosexual
activity or to use a form of effective method of contraception from the time of
informed consent until 30 days after treatment discontinuation.
• 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.
Exclusion Criteria:
• Known hypersensitivity to 5-FU, oxaliplatin or other platinum agents, or any of the
components of nal-IRI and other liposomal products.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not required prior to
enrollment).
• Other active malignancy requiring treatment within the last 2 years. Exceptions
include subjects with non-melanoma skin cancer, non-invasive/in situ cancer or
low-risk prostate cancer requiring hormonal therapy only.
• Current therapy with other investigational agents or participation in another clinical
study (supportive care and nontherapeutic trial participation allowed if not receiving
an investigational drug). Participants may participate in prescreening for other
therapeutic trials (prescreening of biologic sample for specific mutations, receptors,
etc.)
• Major surgery within 28 days or minor surgery within 14 days of the start of the study
treatment, except for tumor biopsy or placement of central infusion device (port
placement).
• Radiotherapy less than 7 days prior to the start of the study treatment
• Participants who receive nivolumab or pembrolizumab in addition to chemotherapy should
not have any contraindications to immune checkpoint inhibitors and should not have
received immunotherapy agents for the treatment of EGA prior to study enrollment.
• Participants must not have active autoimmune disease that has required systemic
treatment in the past 2 years. Participants are permitted to receive
immunotherapy l if they have vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune condition only requiring hormone replacement,
psoriasis not requiring systemic treatment, or conditions not expected to recur
in the absence of an external trigger (precipitating event).
• Participants must not have a condition requiring systemic treatment with either
corticosteroids (>10 mg/day prednisone equivalents) or other immunosuppressive
medications within 14 days of study immunotherapy administration. Inhaled or
topical steroids and adrenal replacement doses (≤10 mg/day prednisone equivalent)
are permitted. Participants with prior immune mediated adverse events related to
immunotherapy that resulted in permanent treatment discontinuation with these
agents.
• Psychological, familial, or sociological condition potentially hampering compliance
with the study protocol and follow-up schedule.
• Active infection requiring systemic therapy.
• Pregnant or breastfeeding.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they
are stable (without evidence of progression by imaging for at least four weeks prior
to the first dose of trial treatment and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis, which is excluded regardless of clinical stability.
• Severe arterial thromboembolic events (myocardial infarction, unstable angina
pectoris, stroke) less than 6 months before inclusion.
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure.
• Known history of Human Immunodeficiency Virus (HIV).
This study is investigating a new administration schedule of Rituximab, Cyclophosphamide,
Doxorubicin, Vincristine, Prednisone (R-CHOP) chemotherapy for participants with Diffuse
Large B-Cell Lymphoma (DLBCL), focusing on an underserved elderly population (aged 75 and up;
certain participants 70-74 may be eligible) that is often excluded from clinical trials.
Participants can expect to be on study for 2.5 years (treatment for 6 months and 2 years of
post treatment follow-up).
Christopher Fletcher, MD
All
70 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03943901
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Inclusion Criteria:
• Signed and dated informed consent document indicating that the participant (or legally
acceptable representative) has been informed of all pertinent aspects of the trial
• All patients age ≥75 years and participants aged 70-74 years who are determined to be
unfit or frail by Cumulative Illness Rating Score-Geriatrics (CIRS-G) scale
• For participants aged 70-74 years: CIRS-G score with 5-8 comorbid conditions
scored 2 or ≥1 comorbidity scored 3-4. CIRS-G score is to be reviewed by the
study PI prior to enrollment.
• Newly diagnosed, untreated, biopsy proven CD20 positive DLBCL (including high grade
B-cell lymphoma & T-cell/histiocytic rich large B-cell lymphoma). Participants with
discordant bone marrow (i.e. involved by low-grade/indolent NHL) are eligible.
Participants with transformed DLBCL from underlying low-grade disease are eligible.
Participants with composite DLBCL and concurrent low-grade lymphoma are eligible.
• Copy of pathology report must be sent to coordinating site to confirm diagnosis
for eligibility
• Participants with prior treatment for low grade NHL with non-anthracycline based
regimens are eligible
• Measurable disease by PET/CT or Bone Marrow (BM) biopsy prior to enrollment
• Left ventricular ejection fraction ≥50% by resting echocardiography or resting
Multi-gated acquisition (MUGA) scan
• Karnofsky Performance Score ≥50
• Ann Arbor Stage II bulky, III, or IV disease
• Minimum life expectancy greater than 3 months
• Negative HIV test
• For participants with hepatitis B virus antigen (HbsAg) or core antibody (HbcAb)
seropositivity, participants must have a negative Hep B viral load and an appropriate
prophylaxis plan must be in place during chemotherapy therapy treatment. For all
participants that have Hep B core antibody positive, they should take entecavir
prophylaxis (0.5 mg PO daily) until 1 year from completion of chemotherapy. Hep B
viral load should be checked on these participants prior to starting chemotherapy and
every 3 months thereafter if initial Hep B viral load is negative (+/- 1 week if
chemotherapy cycle is delayed). If Hep B viral load is positive, Hepatology or
Identification (ID) referral is recommended, and hepatitis B virus (HBV) viral load
should be checked monthly
• For participants with hepatitis C Ab (HbcAb) positivity, a viral load must be checked
and be negative for enrollment
• Intrathecal chemotherapy for central nervous system prophylaxis only can be given at
the discretion of the primary oncologist
Exclusion Criteria:
• History of previous anthracycline exposure
• Central Nervous System (CNS) or meningeal involvement at diagnosis
• Creatinine Clearance <25 mL/min by body surface area (BSA)-adjusted Cockroft-Gault
• Poor hepatic function, defined as total bilirubin concentration greater than 3.0 mg/dL
or transaminases over 4 times the maximum normal concentration, unless these
abnormalities are felt to be related to the lymphoma.
• Pulmonary dysfunction defined as >2 L of oxygen required by nasal cannula to maintain
peripheral capillary oxygen saturation (SpO2) ≥90% unless felt to be related to
underlying lymphoma.
• Myocardial Infarction within 6 months of enrollment
• Active, uncontrolled infectious disease
• Known concurrent bone marrow malignancies (e.g. myelodysplastic syndrome) or poor
bone-marrow reserve, defined as neutrophil count less than 1.5×10⁹/L or platelet count
less than 100×10⁹/L, unless caused by bone-marrow infiltration with lymphoma
• History of a second concurrent active malignancy or prior malignancy which required
chemotherapy treatment within the preceding 2 years
• Treatment with any investigational drug within 30 days before the planned first cycle
of chemotherapy
• Unable or unwilling to sign consent
Non-Hodgkin's Lymphoma, Lymphoma, Diffuse Large B Cell Lymphoma, DLBCL, Cancer
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
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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
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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.
PSMA-based 18F-DCFPyL PET/CT and PET/MRI Pilot Studies in Prostate Cancer
The overall goal of this research is to validate and develop a non-invasive imaging biomarker
of prostate cancer detection, progression, and recurrence. Development of such a biomarker
may be useful to differentiate indolent from aggressive prostate cancer phenotypes allowing
for selection of an appropriate risk adaptive therapy.
Steve Cho
Male
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT03232164
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Inclusion Criteria:
• Prostate cancer pathologically proven by prostate biopsy (newly diagnosed for
Sub-Study 1 and 4)
• Prostate biopsy histology grade ≥ Gleason 1, 6, 3+4, or 4+3; positive biopsy >2 cores
• Any PSA permitted
• Two consecutive rising PSA values (Sub-Study 3 only)
• Castrate-levels of testosterone •total testosterone < 50 ng/dL (Sub-Study 3 only)
• Patients considered as candidates for and medically fit to undergo prostatectomy
• At least 7 days after most recent prostate biopsy
• Imaging evidence of suspected metastatic disease, including CT, bone scan, MRI,
ultrasound or other PET modalities (Sub-Study 3 only)
• New diagnosis of prostate cancer undergoing additional biopsy evaluation (Sub--Study 4
only)
• Karnofsky performance status of at least 70 (Sub-Study 4 only)
• General health and anatomy suitable to undergo transrectal ultrasound-MRI fusion
biopsy of the identified lesions and standard 12 core sextent biopsy (Sub-Study 4
only)
Exclusion Criteria:
• Prior pelvic external beam radiation therapy or brachytherapy
• Chemotherapy for prostate cancer
• Androgen deprivation therapy for prostate cancer
• Investigational therapy for prostate cancer (Sub-Study 3 Only)
• Unable to lie flat during or tolerate PET/CT
• Prior history of any other malignancy within the last 2 years, other than skin basal
cell or cutaneous superficial squamous cell carcinoma that has not metastasized and
superficial bladder cancer.
• No prostatectomy scheduled more than 12 hours post imaging (Sub-Study 1 only)
• Serum creatinine > 2 time the upper limit of normal
• Total bilirubin > 3 times the upper limit of normal
• Liver Transaminases > 5 times the upper limit of normal
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
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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
pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer
This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with
PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and
delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until
radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer.
The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a
greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the
percentage of patients experiencing objective anti-tumor effect as measured by PSA declines
and/or objective radiographic responses. Participants must be 18 years of age or older and
can expect to be on treatment for 2 years (32 cycles) and on study for up to 4 years
(including 2 years of follow up via phone).
Christos Kyriakopoulos, MD
Male
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04090528
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Inclusion Criteria:
• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases
on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All participants must have received (and be receiving) standard of care androgen
deprivation treatment (surgical castration versus GnRH analogue or antagonist
treatment); subjects receiving Gonadotropin-releasing hormone (GnRH) analogue or
antagonist must continue this treatment throughout the time on this study.
• Participants may or may not have been treated previously with a nonsteroidal
antiandrogen. For participants previously treated with an antiandrogen, they must
be off use of anti-androgen for at least 4 weeks (for flutamide, apalutamide,
enzalutamide, or other 2nd generation AR antagonists) or 6 weeks (for
bicalutamide or nilutamide) prior to registration. Moreover, participants who
demonstrate an anti-androgen withdrawal response, defined as a > 25% decline in
PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible
until the PSA rises above the nadir observed after antiandrogen withdrawal.
• Participants must have a castrate serum level of testosterone (< 50 ng/dL) within
6 weeks of day 1
• Progressive disease while receiving androgen deprivation therapy defined by any one of
the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) bone
scan criteria or RECIST 1.1 during or after completing last therapy:
• PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week
intervals, with the final value > 2.0 ng/mL.
• Measurable disease: > 50% increase in the sum of the cross products of all
measurable lesions or the development of new measurable lesions. The short axis
of a target lymph node must be at least 15 mm by spiral CT to be considered a
target lesion
• Non-measurable (bone) disease: The appearance of two or more new areas of uptake
on bone scan (or Sodium Fluoride (NaF) positron emission tomography-computed
tomography (PET/CT)) consistent with metastatic disease compared to previous
imaging during castration therapy. The increased uptake of pre-existing lesions
on bone scan will not be taken to constitute progression, and ambiguous results
must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI).
• Prior treatment with abiraterone or enzalutamide is permitted, but participants must
have weaned to a daily corticosteroid dose equivalent of no more than 5 mg prednisone
daily for at least 28 days prior to day 1.
• Life expectancy of at least 6 months
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1, or 2.
• Adequate hematologic, renal, liver, and coagulation function as evidenced by the
following within 6 weeks of day 1:
• White Blood Cells (WBC) >/= 2000 / mm3
• Absolute Neutrophil Count (ANC) >/= 1500 / mm3
• Hemoglobin (HgB) >/= 9.0 gm/dL (Participants must not have received a blood
transfusion within 14 days)
• Platelets >/= 100,000 / mm3
• Creatinine = 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin = 1.5 x institutional ULN OR direct bilirubin = ULN for
participants with total bilirubin levels > 1.5 x ULN
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) = 2.5 x
institutional upper limit of normal
• Prothrombin Time (PT) or International Normalized Ratio (INR) = 1.5 x ULN
unless participant is receiving anticoagulant therapy and PT is within
therapeutic range of intended use of anticoagulant (only required for
participants receiving biopsy)
• Partial Thromboplastin Time (PTT) = 1.5 x ULN unless participant is receiving
anticoagulant therapy and a PTT is within therapeutic range of intended use of
anticoagulant (only required for participants receiving biopsy)
• No known history of human immunodeficiency viruses (HIV 1 and 2), Human T-cell
leukemia virus type 1 (HTLV-1), or active Hepatitis B or Hepatitis C
• Participants must be at least 4 weeks from any prior treatments and have recovered (to
< Grade 2) from acute toxicity attributed to this prior treatment, unless considered
chronic
• A subset of participants (6 participants per treatment arm) treated at the lead
University of Wisconsin (UW) site must be willing and able (in the opinion of the
treating physician) to undergo two research biopsies for the investigational component
of this trial.
• A subset of participants (6 participants per treatment arm) treated at the lead UW
site must be willing to undergo NaF PET/CT scans for the investigational component of
this trial.
• For those participants who are sexually active, they must be willing to use barrier
contraceptive methods, and refrain from donating sperm, during the period of treatment
on this trial and for four weeks after the last DNA immunization treatment
• Participants must be informed of the experimental nature of the study and its
potential risks, and must sign an Institutional Review Board (IRB)-approved written
informed consent form indicating such an understanding
Exclusion Criteria:
• Small cell or other variant (non-adenocarcinoma) prostate cancer histology, unless
there is evidence that the tumor expresses PAP
• Participants may not be receiving other investigational agents or be receiving
concurrent anticancer therapy other than standard androgen deprivation therapy
• Concurrent bisphosphonate therapy is not excluded, however participants should not
start bisphosphonate therapy while on this study; those participants already receiving
bisphosphonate therapy should continue at the same dosing and schedule as prior to
study entry
• Rapidly progressive symptomatic metastatic disease, as defined by the need for
increased opioid analgesics within one month of registration for the treatment of pain
attributed to a prostate cancer metastatic lesion; participants receiving opioids must
receive approval from the PI for eligibility
• Treatment with any of the following medications within 28 days of day 1, or while on
study, is prohibited:
• Systemic corticosteroids (at doses over the equivalent of 5 mg prednisone daily);
inhaled, intranasal or topical corticosteroids are acceptable
• Prostate Cancer and spes (PC-SPES)
• Megestrol
• Ketoconazole
• 5-α-reductase inhibitors •participants already taking 5-α-reductase inhibitors
prior to 28 days prior to registration may stay on these agents throughout the
course of therapy, but these should not be started while participants are on
study
• Diethyl stilbesterol
• Abiraterone
• Enzalutamide
• Apalutamide
• Radium 223 (Xofigo®)
• Any other hormonal agent or supplement being used with the intent of cancer
treatment must be reviewed by the PI for eligibility
• External beam radiation therapy within 4 weeks of registration is prohibited, or
anticipated need for radiation therapy (e.g. imminent pathological fracture or spinal
cord compression) within 3 months of registration. Participants must have recovered
from all radiation-related toxicities and not have had radiation pneumonitis.
• Major surgery within 4 weeks of registration is prohibited
• Prior cytotoxic chemotherapy (for example, but not limited to, docetaxel,
mitoxantrone, cabazitaxel) within 28 days of registration is prohibited
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with any agent
directed to another T-cell stimulatory or inhibitory receptor (e.g. CTLA-4, OX-40,
CD137).
• Participants with a history of life-threatening autoimmune disease
• Participants with a history of non-infectious pneumonitis that required corticosteroid
treatment, or has current pneumonitis
• Participants with a history of allergic reactions to the tetanus vaccine
• Participants who have undergone splenectomy or who have a diagnosis of
immunodeficiency
• Participants must not have other active malignancies other than non-melanoma skin
cancers or superficial (non-muscle-invasive) carcinoma of the bladder. Participants
with a history of other cancers who have been adequately treated and have been
recurrence-free for > 3 years are eligible.
• Participants with known brain metastases and/or carcinomatous meningitis
• Participants who have received a live vaccine within 30 days prior to the first dose
of study drug. 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 (BCG), and typhoid vaccine. Seasonal influenza
vaccines for injection are generally killed virus vaccines and are allowed; however,
intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not
allowed.
• Any antibiotic therapy within 1 month of day 1, or anticipated need for antibiotic
therapy within 1 month of beginning treatment
• Participants with active autoimmune disease that has required systemic treatment in
the past 2 years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
• Any other medical intervention or condition, which, in the opinion of the PI or
treating physician, could compromise participant safety or adherence with the study
requirements (including biopsies), or confound results of the study, over the
treatment period.
• Any known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirement of the trial.
• Participants cannot have concurrent enrollment on other phase I, II, or III
investigational treatment studies.
Prostate, Castration-resistant Prostate Cancer, Metastatic Cancer, Prostate Cancer
Nivolumab With Ruxolitinib in Relapsed or Refractory Classical Hodgkin Lymphoma
This is a Phase I/II, multicenter, open-label, dose escalation/dose-expansion study to
evaluate the tolerability, safety, and the maximum tolerated dose (MTD) of ruxolitinib when
given with fixed dose nivolumab in patients with relapsed or refractory classical Hodgkin
lymphoma (cHL).
Vaishalee Kenkre, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03681561
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Inclusion Criteria:
• 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.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0, 1 or 2.
• Histologically confirmed diagnosis of classical Hodgkin lymphoma that is relapsed or
refractory •historical biopsy at last relapse is acceptable. NOTE: a repeat biopsy is
not required for Phase I if the historical biopsy was performed at the most recent
relapse, without remission in between. A fresh biopsy is not required for Phase II.
• Presence of radiographically measurable disease (defined as the presence one or more ≥
1.5 cm lesions, as measured in the longest dimension by PET/CT) within 4 weeks of
study registration.
• Prior therapy with check-point inhibitors (nivolumab, pembrolizumab, others) and
subsequent progressive disease, stable disease or mixed response
• Failed at least 2 prior therapies including cytotoxic chemotherapy including ABVD or
similar, autologous transplantation, brentuximab vedotin, allogenic transplantation
without active graft versus host disease Note: Patients who are eligible and willing
to undergo autologous transplant should not be enrolled on this trial
• Prior cancer treatment must be completed at least 14 days prior to registration and
the patient must have recovered from all reversible acute toxic effects of the regimen
(other than alopecia) to ≤Grade 1 or baseline. Radiation therapy must be completed at
least 7 days prior to registration.
• Absolute Neutrophil Count ≥ 1000/μL
• Platelets ≥ 75,000/μL (or ≥50,000/mm3 if known BM involvement)
• Calculated creatinine clearance ≥ 40 cc/min using the Cockcroft-Gault formula
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 × ULN
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN
• 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
• Males who are sexually active with partners of child-bearing potential must be willing
to abstain from heterosexual activity or adhere to contraception from the time of
written consent until 7 months after treatment discontinuation.
• Patient must provide voluntary written informed consent prior to the performance of
any research related tests or procedures.
Exclusion Criteria:
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
• Inability or unwillingness to swallow oral medication or any condition that precludes
the administration and/or absorption of oral medications
• A life-threatening illness, medical condition or organ system dysfunction, which in
the investigator's opinion, could compromise the patient's safety, interfere with the
metabolism of study drugs, or put the study outcomes at undue risk
• Active central nervous system (CNS) involvement by lymphoma
• Uncontrolled cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, or myocardial infarction or any class 3 or 4 cardiac disease
as defined by the New York Heart Association Functional Classification
• Concomitant therapy with immunosuppressive agents, including systemic corticosteroids
(doses ≤ 10 mg/day prednisone or equivalent are permitted).
• Has a history of autoimmune disease now or in past 3 years such as hepatitis,
nephritis, hyperthyroidism, interstitial lung disease or colitis except vitiligo or
alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months of registration are eligible for this trial.
• Active Hepatitis B or C infection (defined as a positive Hepatitis B surface antigen
(Ag) or detectable viral load by PCR). NOTES: Hepatitis B and C testing is required.
Patients with positive Hepatitis B Ag may enroll if PCR is negative. Suppressive
antiviral therapy should be considered for these patients as clinically indicated.
• Currently active, clinically significant hepatic impairment Child-Pugh class B or C
• Currently receiving a strong CYP3A4 Inhibitor (such as but not limited to boceprevir
clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole,
lopinavir/ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir,
saquinavir, telaprevir, telithromycin, voriconazole) or Fluconazole >200 mg/day.
Washout period of 1 week is required.
• History of stroke or intracranial hemorrhage within 6 months of study registration
Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-positive Salivary Gland Carcinoma
A Phase II, multi-center, single-arm, non-blinded study combining androgen deprivation
therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen
receptor-positive salivary gland carcinoma, not amenable to surgery or radiation.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03942653
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Inclusion Criteria:
• 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.
• Age ≥ 18 years at the time of consent.
• Locally advanced, recurrent, or metastatic salivary gland carcinoma that is not
amenable to curative surgery or radiation
• ECOG Performance Status of 0 or 1 within 28 days prior to registration.
• Local, pathologic testing of androgen receptor-positive salivary gland carcinoma will
be performed as standard of care. Archival tissue must be available for central
confirmation of androgen receptor-positive disease and for correlative studies. AR
positivity will be defined according to IHC staining of tumor tissue with at least 20%
of tumor staining positive with moderate intensity (1+ or greater).
• Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to
registration.
• For patients who have been treated with prior therapy, patients must have documented
progression of disease on their prior therapy for entry into the study.
• Patients with prior chemotherapy, radiation, or surgery as part of curative intent
therapy are allowed. Any number of prior lines of systemic therapy is permitted for
entry into this study so long as prior therapy did not include anti-androgen therapy
or immune checkpoint blockade.
• If prior cancer treatment, the subject must have recovered from toxic effects of prior
cancer treatment (other than alopecia) to ≤ Grade 1.
• Adequate organ function as defined below; all screening labs to be obtained within 28
days prior to registration.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100,000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
• Creatinine (Cr) OR Measured or calculated creatinine clearance (GFR can also be
used in place of Cr or creatinine clearance) ≤1.5 × ULN OR
≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total
bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver
metastases) o International normalized ratio (INR) OR prothrombin time (PT) &
aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as
PT or aPTT is within therapeutic range of intended use of anticoagulants
• A male participant must agree to use contraception during the treatment period and for
at least 8 months after the last dose of study treatment and refrain from donating
sperm during this period.
• Females of childbearing potential must have a negative serum pregnancy test within 72
hours 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
• Females of childbearing potential and males with partners of childbearing potential
must be willing to abstain from heterosexual activity or to use a highly effect form
of contraception from the time of informed consent until 8 months after treatment
discontinuation.
• 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
Exclusion Criteria:
• Women of childbearing age with a positive serum pregnancy test within 72 hours prior
to study registration.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX40, CD137).
• Has received prior androgen deprivation therapy including orchiectomy,
gonadotropin-releasing hormone (GnRH) agonists/antagonists, androgen receptor blocker,
abiraterone, or enzalutamide.
• Has received prior systemic anti-cancer therapy including investigational agents
within 14 days prior to registration.
• Has had an allogenic tissue or solid organ transplant.
• Has received prior palliative radiotherapy within 7 days of start of study treatment.
Participants must have recovered from all radiation-related toxicities and require
less than 10mg of prednisone (or equivalent corticosteroid) daily.
• Has received a live vaccine or live-attenuated vaccine within 28 days prior to the
first dose of study drug. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast ductal
carcinoma in situ, cervical cancer in situ) that have undergone potentially curative
therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 14 days by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable, and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment.
• Has ≥Grade 3 hypersensitivity to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg, levothyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has a known history of active TB (Bacillus Tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
Lip, Oral Cavity and Pharynx, Head and Neck, Salivary Gland Carcinoma
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
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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.
Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)
The study evaluates CLR 131 in children, adolescents, and young adults with relapsed or
refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain
tumors for which there are no standard treatment options with curative potential.
Nicholas Pytel, DO
All
2 Years to 25 Years old
Phase 1
This study is NOT accepting healthy volunteers
NCT03478462
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Inclusion Criteria:
All Patients
• Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g.,
neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain
tumors that are clinically or radiographically suspected to be relapsed, refractory,
or recurrent for which there are no standard treatment options with curative
potential. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll
without histological or cytological confirmation.
• ≥ 2 years of age and ≤ 25 years of age at time of consent/assent
• If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky
performance status ≥ 60
• Platelets ≥ 75,000/µL (last transfusion, if any, must be at least 1 week prior to
study registration, and, unless deemed medically necessary, no transfusions are
allowed between registration and dosing)
• Absolute neutrophil count ≥ 750/µL
• Hemoglobin ≥ 8 g/dL (last transfusion must be at least 1 week prior to study
registration, and, unless deemed medically necessary, no transfusions are allowed
between registration and dosing)
• Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60
ml/min/1.73m2
• Alanine aminotransferase < 3 × ULN
• Bilirubin < 2 × ULN
• Patients who have undergone autologous or allogeneic bone marrow transplant must be at
least 3 months from transplant.
• Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have
availability or ability to collect an autologous hematopoietic stem cell back-up
product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+
cells must be available.
• Patient or his or her legal representative is judged by the Investigator to have the
initiative and means to be compliant with the protocol.
Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 mm. Patients with a
lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron
emission tomography (PET) positive may be enrolled at the investigator's discretion,
even if not associated with a measurable lesion of at least 10 mm. Patients with
neuroblastoma who have detectable disease may enroll provided they meet the
requirements of the International Neuroblastoma Response Criteria.
• Patients with known brain metastases must have completed any radiotherapy or systemic
treatments for brain metastases prior to enrollment; by investigator assessment be
considered stable with no new signs or symptoms for at least 1 month, and on a stable
dose of steroids (unchanged for three weeks prior to registration or on a steroid
tapering regimen).
Patients with Recurrent or Refractory Brain Tumors
• At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging
sequence.
• Patients with previously known neurological deficits must be clinically stable at time
of enrollment and able to complete all study related procedures. Patients with
documented or newly diagnosed neurological deficits will be enrolled at the
investigator's discretion.
• If patient receives steroids for neurological symptom control, the dose must be stable
(unchanged for three weeks prior to registration) or on a steroid tapering regimen.
Initiation of steroids per routine care immediately prior to CLR 131 dosing is
acceptable.
Exclusion Criteria:
• Patients receiving active treatment for central nervous system metastases or those
that are likely to require active treatment during anticipated participation in this
trial. Patients with stable brain metastases treated with steroids may enroll at the
investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless
previously treated with surgery, systemic therapy, or radiotherapy with the patient
neurologically stable. Patients with metastatic brain tumors that have been previously
treated are allowed, provided the patient is neurologically stable (determined at the
investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. For certain
types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to
skull-based metastases is not considered craniospinal radiation for the purposes of
this study]), at least 3 months must have elapsed. No washout is required for
palliative focal radiation. NOTE: Patients participating in non-interventional
clinical trials (i.e., non-drug) are allowed to participate in this trial
• Patients previously treated with iodine-131 (131I)-MIBG who have already received a
cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in
this trial, are not eligible.
Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab
followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by
nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread
to other parts of the body. The addition of cabozantinib to the usual treatment may make it
work better. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of
the enzymes needed for cell growth. It is not yet known how well the combination of
cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in
treating patients with renal cell cancer that has spread to other parts of the body.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03793166
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Inclusion Criteria:
• STEP I REGISTRATION CRITERIA
• Histologically documented renal cell carcinoma with clear cell component, including
patients who have sarcomatoid or rhabdoid features
• Any metastatic disease, including visceral, lymph node, other soft tissue and bone,
measurable per RECIST 1.1.
• Measurable disease as defined in the protocol.
• Must be intermediate or poor risk patient per International Metastatic Renal Cell
Carcinoma Database (IMDC) criteria (1 or more of the following): Karnofsky performance
status [KPS] < 80, < 1 year from diagnosis [including initial nephrectomy] to systemic
treatment for metastatic disease, hemoglobin less than lower limit of normal [LLN],
corrected calcium concentration greater than upper limit of normal [ULN], absolute
neutrophil count greater than ULN, platelet count > ULN).
• Central nervous system (CNS) disease permitted, if stable and not otherwise causing
symptoms or needing active treatment.
• Karnofsky performance status >= 70%.
• No prior treatment with PD-1, PD-L1, or CTLA-4 targeting agents (including but not
limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab,
tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting
T-cell co-stimulation or checkpoint pathways. The only exception is for prior
treatment with nivolumab or other PD-1/PD-L1/CTLA-4 targeting therapy on pre- or
post-operative trials, as long as > 1 year since completion of systemic therapy.
• No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [> 28 days]
and prior adjuvant sunitinib > 180 days since completion and prior immunotherapy as
above are allowed).
• No systemic cancer therapy less than 28 days prior to registration; no radiation
therapy less than 14 days prior to registration. There must be a complete recovery and
no ongoing complications from radiotherapy.
• 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 or urine pregnancy test done =< 14 days prior to
registration is required.
• Age >= 18 years
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Hemoglobin >= 8 g/dL.
• Calculated (Calc.) creatinine clearance >= 30 mL/min.
• Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with known
or likely Gilbert's syndrome, for whom total bilirubin up to 3 mg/dL is allowed with
direct bilirubin =< 20% total bilirubin)
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) =< 2.5 x upper limit of
normal (ULN) or < 5 x ULN if hepatic metastases present.
• STEP 2 REGISTRATION ELIGIBILITY CRITERIA
• Successful completion of at least 1 cycle of ipilimumab/nivolumab.
• Resolution of any treatment-related adverse events to grade 1 or less per dose
modification section (this criteria does not include any adverse events [AEs] not
attributable to treatment which are present due to disease), with
prednisone-equivalent dosing at 10 mg daily or less. Exceptions for this criteria
include patients receiving replacement hormone treatments (such as levothyroxine for
treatment-related hypothyroidism or glucocorticoid replacement for adrenal
insufficiency). Please contact study chair if further discussion is needed.
• No more than 80 days from last dose of ipilimumab/nivolumab.
Exclusion Criteria:
• Active autoimmune disease requiring ongoing therapy.
• Ongoing acute toxicity > grade 2 from previous treatment.
• History of severe allergic, anaphylactic or other hypersensitivity reactions to
chimeric or humanized antibodies.
• Active hepatitis B/C, or active tuberculosis (PPD response without active TB is
allowed)
• Human immunodeficiency virus (HIV) -infected patients with detectable viral load
within 6 months prior to registration. Patients on effective anti-retroviral therapy
with undetectable viral load within 6 months prior to registration are eligible.
• Concurrent use of immunosuppressive medication including prednisone above 10 mg daily.
• Uncontrolled adrenal insufficiency.
• Uncontrolled hypertension (systolic blood pressure [BP] >150 mmHg or diastolic BP > 90
mmHg).
• Major surgery less than 28 days prior to registration.
• Any serious non-healing wound, ulcer, or bone fracture within 28 days prior to
registration.
• Any arterial thrombotic events within 180 days prior to registration.
• Clinically significant hematuria, hematemesis, or hemoptysis within 12 weeks prior to
registration.
• Cavitating pulmonary lesions or known endotracheal or endobronchial disease
manifestations.
• Lesions encasing or invading any major blood vessels (this does not include tumor
thrombus extending into/through renal vein/inferior vena cava [IVC]). Patients with
tumor thrombus extending into/through renal vein are considered eligible.
• Moderate of severe hepatic impairment (Child-Pugh B or C).
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) in the 180
days prior to registration. (Any asymptomatic, treated pulmonary embolism or
asymptomatic, treated deep venous thrombosis > 30 days prior to registration allowed).
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms.
• Unstable cardiac arrhythmia within 6 months prior to registration.
• Any gastrointestinal (GI) bleeding =< 180 days, hemoptysis, or other signs of
pulmonary hemorrhage =< 90 days prior to registration.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess,
bowel obstruction, or gastric outlet obstruction within 180 days prior to
registration.
• Active peptic ulcer disease, inflammatory bowel disease, or malabsorption syndrome
within 28 days prior to registration.
• Untreated hypothyroidism (treated hypothyroidism on thyroid replacement therapy is
allowed. Abnormal thyroid-stimulating hormone (TSH) is acceptable with normal T3/free
T4 if treated on thyroid replacement therapy)
• Evidence of pancreatitis, history of organ transplant, or history of congenital QT
syndrome.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors
(e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g.,
clopidogrel) within 5 days of registration. Allowed anticoagulants include:
prophylactic use of low-dose aspirin for cardio-protection (per local applicable
guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of
LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban,
apixaban. Allowed also in patients with known brain metastases who are on a stable
dose of the anticoagulant for at least 1 week prior to registration without clinically
significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Significant cardiac ischemia events (ST elevation myocardial infarction [STEMI] or
non-ST elevation myocardial infarction [NSTEMI]) within 6 months or active NY Heart
Association class 3-4 heart failure symptoms
Kidney, Clear Cell Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Metastatic Malignant Neoplasm in the Lymph Nodes, Metastatic Malignant Neoplasm in the Soft Tissues, Metastatic Malignant Neoplasm in the Viscera, Sarcomatoid Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8
Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
This randomized phase III trial studies how well crizotinib works in treating patients with
stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation
in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make
it very active and important for tumor cell growth and progression. Crizotinib may stop the
growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an
effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.
Kari Wisinski, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT02201992
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Inclusion Criteria:
• Patients must have undergone complete surgical resection of their stage IB (>= 4 cm),
II, or non-squamous IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th
edition and have had negative margins; N3 disease is not allowed
• Baseline chest computed tomography (CT) with or without contrast must be performed
within 6 months (180 days) prior to randomization to ensure no evidence of disease; if
clinically indicated additional imaging studies must be performed to rule out
metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to
randomization
• Positive for translocation or inversion events involving the ALK gene locus (e.g.
resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as
determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay
and defined by an increase in the distance between 5? and 3? ALK probes or the loss of
the 5? probe; this must have been performed:
• By a local Clinical Laboratory Improvement Amendments (CLIA) certified
laboratory: report must indicate the results as well as the CLIA number of the
laboratory which performed the assay; tissue must be available for submission for
central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN
(ALLIANCE A151216) OR
• Patient registered to and the ALK fusion status performed centrally on the
ALCHEMIST-SCREEN (ALLIANCE A151216)
• Women must not be pregnant or breast-feeding
• All females of childbearing potential must have a blood or urine pregnancy test within
72 hours prior to randomization to rule out pregnancy; a female of childbearing
potential is any woman, regardless of sexual orientation or whether they have
undergone tubal ligation, who meets the following criteria: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
for at least 24 consecutive months (i.e., has had menses at any time in the preceding
24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to
practice abstinence or use an accepted and effective method of contraception
• Patients must NOT have uncontrolled intercurrent illness including, but not limited
to, serious ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements
• No known interstitial fibrosis or interstitial lung disease
• No prior treatment with crizotinib or another ALK inhibitor
• No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial
fibrillation (any grade), or corrected QT (QTc) interval > 470 msec
• No use of medications, herbals, or foods that are known potent cytochrome P450,
subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited
to those outlined
• Patients must be adequately recovered from surgery at the time of randomization
• The minimum time requirement between date of surgery and randomization must be at
least 4 weeks (28 days)
• The maximum time requirement between surgery and randomization must be:
• 3 months (90 days) if no adjuvant chemotherapy was administered
• 8 months (240 days) if adjuvant chemotherapy was administered
• 10 months (300 days) if adjuvant chemotherapy and radiation therapy were
administered
• Patients must have completed any prior adjuvant chemotherapy or radiation therapy 2 or
more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and
be adequately recovered at the time of randomization
• NOTE: Patients taking low dose methotrexate for non-malignant conditions and
other cytotoxic agents for non-malignant conditions are allowed to continue
treatment while on study
• NOTE: Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer
is not permitted
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) =< 2.5
x upper limit of normal (ULN)
• Total serum bilirubin =< 1.5 x ULN
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 30,000/mm^3
• Hemoglobin >= 8.0 g/dL
• Serum creatinine =< 2 x ULN
• Prior to randomization patients with any non-hematologic toxicity from surgery,
chemotherapy, or radiation must have recovered to grade =< 1 with the exception of
alopecia and the criteria outlined
• Patients must not have any history of locally advanced or metastatic cancer requiring
systemic therapy within 5 years from randomization, with the exception of in-situ
carcinomas and non-melanoma skin cancer; patients must have no previous primary lung
cancer diagnosed concurrently or within the past 2 years
• Patients may not be receiving any other investigational agents while on study
Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA
non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in
a patient's tumor cells may help doctors select the best treatment for patients that have
certain genetic changes.
Kari Wisinski, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT02194738
Show full eligibility criteria
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Inclusion Criteria:
• PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
• For pre-surgical patients
• Suspected diagnosis of resectable non-small cell lung cancer; cancers with a
histology of "adenosquamous" are considered a type of adenocarcinoma and thus a
"nonsquamous" histology; patients with squamous cell carcinoma are eligible
• Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size >=
4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural
invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of
American Joint Committee on Cancer (AJCC) staging will be utilized
• For post-surgical patients
• Completely resected non-small cell lung cancer with negative margins (R0);
patients with squamous cell carcinoma are eligible only if they have not received
adjuvant therapy
• Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm);
Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural
invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of
AJCC staging will be utilized
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Age ≥ 18 years
• No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this
lung cancer
• No locally advanced or metastatic cancer requiring systemic therapy within 5 years
prior to registration; no secondary primary lung cancer diagnosed concurrently or
within 2 year prior to registration
• No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and
PD-1/PD-L1/CTLA-4
• No patients known to be pregnant or lactating
• Patients who have had local genotyping are eligible, regardless of the local result
• No patients with recurrence of lung cancer after prior resection
• Note: Post-surgical patients should proceed to registration immediately following
preregistration
• PATIENT REGISTRATION ELIGIBILITY CRITERIA:
• Tissue available for the required analyses (either clinical tissue block or slides and
scrolls)
• Completely resected NSCLC with negative margins (R0); cancers with a histology of
"adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous"
histology
• Pathologic stage IIIA, IIA or IIB, or large IB (defined as size >= 4 cm); Note: IB
tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not
eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be
utilized
• Patients with squamous cell carcinoma are eligible only if they have not received
adjuvant therapy
• In order to allow for time for central genotyping and eligibility for the ALCHEMIST
treatment trial, patients must register within the following eligibility windows:
• Squamous patients:
• No adjuvant therapy permitted, register patient within 77 days following
surgery
• Non-squamous patients:
• If no adjuvant therapy, register patient within 75 days following surgery
• If adjuvant chemotherapy or radiotherapy only, register patient within 225
days following surgery
• If adjuvant chemotherapy and radiation, register patient within 285 days
following surgery
Lung, Stage IB Lung Non-Small Cell Carcinoma AJCC v7, Stage II Lung Non-Small Cell Cancer AJCC v7, Stage IIA Lung Cancer AJCC v8, Stage IIB Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Cancer AJCC v8
Long-Term Follow-up Protocol for Participants Treated With Gene-Modified T Cells
This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all
pediatric and adult participants exposed to Gene-modified (GM) T cell therapy participating
in a previous Celgene sponsored or Celgene alliance partner sponsored study.
Participants who received at least one GM T cell infusion will be asked to enroll in this
LTFU protocol upon either premature discontinuation from, or completion of the prior parent
treatment protocol.
Natalie Callander, MD
All
Not specified
Phase 2/Phase 3
This study is NOT accepting healthy volunteers
NCT03435796
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Inclusion Criteria:
• Received at least one gene-modified (GM) T-cell infusion in a previous Celgene
sponsored or Celgene alliance partner-sponsored study, and have discontinued, or
completed the post-treatment follow-up period in the parent treatment protocol, as
applicable.
• Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form
prior to any study-related assessments/procedures being conducted.
Exclusion Criteria:
Not Applicable
Other protocol-defined inclusion/exclusion criteria apply
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
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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
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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
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction
chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
pegaspargase or calaspargase pegol 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 will also study the outcomes of patients with mixed phenotype acute
leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk
ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
Induction and Consolidation. This part will collect information on the leukemia, as well as
the effects of the initial treatment, to classify patients into post-consolidation treatment
groups. On the second part of this study, patients with HR B-ALL will receive the remainder
of the chemotherapy cycles (interim maintenance I, delayed intensification, interim
maintenance II, maintenance), with some patients randomized to receive inotuzumab. The
patients that receive inotuzumab will not receive part of delayed intensification. Other aims
of this study include investigating whether treating both males and females with the same
duration of chemotherapy maintains outcomes for males who have previously been treated for an
additional year compared to girls, as well as to evaluate the best ways to help patients
adhere to oral chemotherapy regimens. Finally, this study will be the first to track the
outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed
Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Kenneth Desantes, M.D.
All
1 Year to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03959085
Show full eligibility criteria
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Inclusion Criteria:
• B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected
MPAL patients. If not performed within this time frame, patients will be taken off
protocol.
• APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
every patient should be offered participation in APEC14B1. B-LLy patients may directly
enroll on AALL1732.
• Patients must be > 365 days and < 25 years of age
• White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-9.99 years: WBC >= 50,000/uL
• Age 10-24.99 years: Any WBC
• Age 1-9.99 years: WBC < 50,000/uL with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment.
• White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
the start of protocol-directed systemic therapy):
• Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on
central confirmatory testing to have B-ALL must meet the B-ALL criteria above
(age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL
stratum before the end of induction.
• Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
criteria) with >= 25% blasts on a bone marrow (BM) aspirate;
• OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
biopsy;
• OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
performed.
• Patient has newly diagnosed B-LLy Murphy stages III or IV.
• Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
paraffin blocks), the methodology and criteria for immunophenotypic analysis to
establish the diagnosis of B-LLy defined by the submitting institution will be
accepted.
• Central nervous system (CNS) status must be determined prior to enrollment based on a
sample obtained prior to administration of any systemic or intrathecal chemotherapy,
except for steroid pretreatment and cytoreduction. It is recommended that intrathecal
cytarabine be administered at the time of the diagnostic lumbar puncture. This is
usually done at the time of the diagnostic bone marrow or venous line placement to
avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic
chemotherapy must begin within 72 hours of this intrathecal therapy.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met.
Exclusion Criteria:
• Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
are eligible for AALL1731, regardless of NCI risk group).
• With the exception of steroid pretreatment and steroid cytoreduction or the
administration of intrathecal cytarabine, patients must not have received any prior
cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any
cancer diagnosed prior to initiation of protocol therapy on AALL1732.
• Patients who have received > 72 hours of hydroxyurea within one week prior to start of
systemic protocol therapy.
• Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patients with acute undifferentiated leukemia (AUL) are not eligible.
• For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
pretreatment, the following additional exclusion criteria apply:
• T-lymphoblastic lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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 women who plan to breastfeed their infants while on study and for 2 months
after the last dose of inotuzumab ozogamicin.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of study participation. For those
patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
inotuzumab ozogamicin for males.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in
treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or
B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as
blinatumomab, may induce changes in the body's immune system and may interfere with the
ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine,
dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine,
mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, 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. Leucovorin decreases the toxic effects of methotrexate.
Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving
blinatumomab and combination chemotherapy may work better than combination chemotherapy alone
in treating patients with B-ALL. This trial also assigns patients into different chemotherapy
treatment regimens based on risk (the chance of cancer returning after treatment). Treating
patients with chemotherapy based on risk may help doctors decide which patients can best
benefit from which chemotherapy treatment regimens.
Kenneth Desantes, M.D.
All
365 Days to 31 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03914625
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
(Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
(performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell
count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion
for diagnosis should be analogous to B-ALL. For tissue processed by other means
(i.e., paraffin blocks), the methodology and criteria for immunophenotypic
analysis to establish the diagnosis of B-LLy defined by the submitting
institution will be accepted (diagnostic biopsy for B-LLy must be performed
within 14 days prior to enrollment).
• 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:
• Patient must not have secondary ALL that developed after treatment of a prior
malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
history of transient myeloproliferative disease (TMD) are not considered to have had a
prior malignancy. They would therefore be eligible whether or not the TMD was treated
with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion
criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in
the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to
the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the
DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
to administration of any systemic or intrathecal chemotherapy, except for steroid
pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% •25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• 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.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Down Syndrome, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
This phase II trial studies how stopping tyrosine kinase inhibitors will affect
treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the
level of disease is very low, it's called molecular remission. TKIs are a type of medication
that help keep this level low. However, after being in molecular remission for a specific
amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet
known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid
leukemia in chronic phase continue or re-achieve molecular remission.
Kenneth Desantes, M.D.
All
up to 25 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03817398
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patient must have been diagnosed with CML-CP at < 18 years of age.
• Patient must have histologic verification of CML-CP at original diagnosis
• Patient must be in molecular remission (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1
as measured using the International Scale (IS) by RQ-PCR for >= 2 consecutive years at
the time of enrollment
• Please note: The lab evaluating disease status and molecular response for this
study must be College of American Pathology (CAP) and/or Clinical Laboratory
Improvement Amendments (CLIA) certified (United States [US] only), sites in other
countries must be certified by their accredited authorities. All labs must use
the International Scale guidelines with a sensitivity of detection assay =< 0.01%
BCR-ABL1 and be able to report results in =< 2 weeks
• Patient must have received any TKI for a minimum of 3 consecutive years at time of
enrollment
• Patient agrees to discontinue TKI therapy
• REGULATORY REQUIREMENTS
• 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
• ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
• Age >= 8 years at the time of enrollment
• Ability to understand English or Spanish
• Cognitive ability to complete instruments according to the primary team
• ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
• Patient must be 5 years or older at the time of enrollment
• English-, French- or Spanish-speaking
• No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down
syndrome, Fragile X, William syndrome, mental retardation)
• No significant visual or motor impairment that would prevent computer use or
recognition of visual test stimuli
Exclusion Criteria:
• Known T3151 mutation
• Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive
(+) cells at any time prior to enrollment that include "major route" abnormalities
(second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or
abnormalities of 3q26.2
• History of accelerated phase or blast crisis CML
• Female patients who are pregnant
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained
Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
This study will evaluate the safety, tolerability, drug levels, molecular effects, and
clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a
KRAS G12C mutation.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT03785249
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease
• Standard treatment is not available or patient declines; first-line treatment for
NSCLC for certain cohorts
• Adequate organ function
Exclusion Criteria:
• History of intestinal disease or major gastric surgery or inability to swallow oral
medications
• Other active cancer
The investigators want to study if lower doses of chemotherapy will help babies with SCID to
achieve good immunity with less short and long-term risks of complications after
transplantation. This trial identifies babies with types of immune deficiencies that are most
likely to succeed with this approach and offers them transplant early in life before they get
severe infections or later if their infections are under control. It includes only patients
receiving unrelated or mismatched related donor transplants.
The study will test if patients receiving transplant using either a low dose busulfan or a
medium dose busulfan will have immune recovery of both T and B cells, measured by the ability
to respond to immunizations after transplant. The exact regimen depends on the subtype of
SCID the patient has. Donors used for transplant must be unrelated or half-matched related
(haploidentical) donors, and peripheral blood stem cells must be used. To minimize the chance
of graft-versus-host disease (GVHD), the stem cells will have most, but not all, of the T
cells removed, using a newer, experimental approach of a well-established technology. Once
the stem cell transplant is completed, patients will be followed for 3 years. Approximately
9-18 months after the transplant, vaccinations will be administered, and a blood test
measuring whether your child's body has responded to the vaccine will be collected.
Kenneth Desantes, M.D.
All
0 Years to 2 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT03619551
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Infants with SCID, either typical or leaky or Omenn syndrome.
1. Typical SCID is defined as either of the following
• Absence or very low number of T cells (CD3+ T cells <300/microliter AND no or
very low T cell function (<10% of lower limit of normal) as measured by response
to phytohemagglutinin OR
• Presence of maternally derived T cells
2. Leaky SCID is defined as the following
• Absence of maternally derived T cells
• AND either one or both of the following (i, ii): i) <50% of lower limit of normal T
cell function as measured by response to PHA OR <30% of lower limit of normal T cell
function as measured by response to CD3 ii) Absent or <10% of lower limit of normal
proliferative responses to candida and tetanus toxoid antigens (must document post
vaccination or exposure for this criterion to apply)
• AND at least two of the following (i through iii): i) CD3 T cells < 1500/microliter
ii) >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (at < 4 years of
age) AND/OR are oligoclonal T iii) Low TRECs and/or the percentage of CD4+/45RA+/CD31+
or CD4+/45RA+/CD62L+ cells is below the lower level of normal.
3. Omenn syndrome • Generalized skin rash
• Maternal lymphocytes tested for and not detected.
• >80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR >80% of CD3+ or CD4+ T cells are
CD62L negative AND/OR >50% of CD3+ or CD4+ T cells express HLA-DR (<2 years of
age)
• Absent or low (up to 30% lower limit of normal (LLN)) T cell proliferation to
antigens (Candida, tetanus) to which the patient has been exposed IF:
Proliferation to antigen was not performed, but at least 4 of the following 8
supportive criteria, at least one of which must be among those marked with an
asterisk (*) below are present, the patient is eligible as Omenn Syndrome.
1. Hepatomegaly
2. Splenomegaly
3. Lymphadenopathy
4. Elevated IgE
5. Elevated absolute eosinophil count
6. *Oligoclonal T cells measured by CDR3 length or flow cytometry (upload
report)
7. *Proliferation to PHA is reduced to < 50% of lower limit of normal (LLN) or
SI < 30
8. *Low TRECs and/or percentage of CD4+/RA+ CD31+ or CD4+/RA+ CD62L+ cells
below the lower level of normal
2. Documented mutation in one of the following SCID-related genes
a. Cytokine receptor defects (IL2RG, JAK3) b. T cell receptor rearrangement defects (RAG1,
RAG2) 3. No available genotypically matched related donor (sibling) 4. Availability of a
suitable donor and graft source
1. Haploidentical related mobilized peripheral blood cells
2. 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor
mobilized peripheral blood cells 5. Age 0 to 2 years at enrollment
Note: to ensure appropriate hepatic metabolism, age at time of busulfan start:
For IL2RG/JAK3: 8 weeks For RAG1/RAG2: 12 weeks
6. Adequate organ function defined as:
1. Cardiac:
Left ventricular ejection fraction (LVEF) at rest ≥ 40% or, shortening fraction (SF) ≥
26% by echocardiogram.
2. Hepatic:
Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have
been diagnosed with Gilbert's Disease are allowed to exceed this limit) and AST and
ALT < 5.0 x ULN for age.
3. Renal:
GFR estimated by the updated Schwartz formula ≥ 90 mL/min/1.73 m2. If the estimated
GFR is < 90 mL/min/1.73 m2, then renal function must be measured by 24-hour creatinine
clearance or nuclear GFR, and must be > 50 mL/min/1.73 m2.
4. Pulmonary No need for supplemental oxygen and O2 saturation > 92% on room air at sea
level (with lower levels allowed at higher elevations per established center standard
of care).
Exclusion Criteria:
1. Presence of any serious life-threatening or opportunistic infection at time of
enrollment and prior to the initiation of the preparative regimen. Serious infections
as defined below that occur after enrollment must be reported immediately to the Study
Coordinating Center, and enrollment will be put on hold until the infection resolves.
Ideally enrolled subjects will not have had any infection. If patients have
experienced infections, these must have resolved by the following definitions:
a. Bacterial i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site must be negative and patient has completed appropriate
course of antibacterial therapy (typically at least 10 days).
ii. Tissue-based clinical infection (e.g. cellulitis): Complete resolution of clinical
signs (e.g. erythema, tenderness, etc.) and patient has completed appropriate course
of antibacterial therapy (typically at least 10 days).
iii. Pneumonia, organism not identified by bronchoalveolar lavage: Complete resolution
of clinical signs (e.g. tachypnea, oxygen requirement, etc.) and patient has completed
appropriate course of antibacterial therapy (typically at least 10 days). If possible,
radiographic resolution should also be demonstrated.
b. Fungal i. Positive culture from a sterile site (e.g. blood, CSF, etc.): Repeat
culture(s) from same site is negative and patient has completed appropriate course of
antifungal therapy (typically at least 14 days). The patient may be continued on
antifungal prophylaxis following completion of the treatment course.
c. Pneumocystis i. Complete resolution of clinical signs (e.g. tachypnea, oxygen
requirement, etc.) and patient has completed appropriate course of therapy (typically
at least 21 days). If possible, radiographic resolution should also be demonstrated.
The patient may be continued on prophylaxis following completion of the treatment
course.
d. Viral i. Viral PCRs from previously documented sites (blood, nasopharynx, CSF) must
be re-tested and are negative.
ii. If re-sampling a site is not clinically feasible (i.e. BAL fluid): Complete
resolution of clinical signs (e.g. tachypnea, oxygen requirement, etc.). If possible,
radiographic resolution should also be demonstrated.
2. Patients with HIV or HTLV I/II infection will be excluded.
SCID, Other Hematopoietic, Unknown Sites, Hematologic cancers, other
Study of Sacituzumab Govitecan in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread (TROPHY U-01)
The objective of this study is to evaluate the efficacy and safety of sacituzumab
govitecan-hziy monotherapy and with novel combinations in participants with metastatic
urothelial cancer (mUC).
Christos Kyriakopoulos, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03547973
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Key
Inclusion Criteria:
• Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
• Individuals with histologically confirmed urothelial cancer (UC).
• Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
• Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of
platinum-containing regimen (cisplatin or carboplatin):
• Received a first-line platinum-containing regimen in the metastatic setting or
for inoperable locally advanced disease;
• Or received neo/adjuvant platinum-containing therapy for localized
muscle-invasive urothelial cancer, with recurrence/progression ≤12 months
following completion of therapy.
• Cohort 1: In addition to above criterion, have had progression or recurrence of
urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1
(anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
• Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease
and have had progression or recurrence of urothelial cancer after a first-line therapy
for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received
any platinum for treatment of recurrent, metastatic or advanced disease.
• Cohort 3: Progression or recurrence of UC following a platinum containing regimen in
the metastatic setting, or progression or recurrence of UC within 12 months of
completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
• Cohort 4: Individual has not received any platinum-based chemotherapy in the
metastatic or unresectable locally advanced setting. Creatinine clearance of at least
50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For
individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a
creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or
another validated tool is required. Individuals with creatinine clearance between 50
to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of
every 21-day cycle).
• Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic
urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
• Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM +
cisplatin. No other chemotherapy regimens are allowed in this cohort, with the
exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after
> 12 months from completion of therapy.
• No evidence of progressive disease following completion of first-line
chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
• Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
• Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for
unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12
months from completion of adjuvant therapy are permitted.
• Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria.
Tumor lesions situated in a previously irradiated area are considered measurable if
progression has been demonstrated in such lesions.
• Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the
Cockcroft-Gault formula unless otherwise specified
• Adequate renal and hepatic function.
• Adequate hematologic parameters without transfusional support.
• Individuals must have a 3-month life expectancy.
Key
Exclusion Criteria:
• Females who are pregnant or lactating.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (ie, ≤Grade 1 from AEs
due to a previously administered agent).
• For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade < 2
adverse events not constituting a safety risk based on the investigator's judgment are
acceptable.
• Requires concomitant medication interfering with UGT1A1 with no alternate option
available.
• Has an active second malignancy.
• Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.
• Has known active Hepatitis B or Hepatitis C.
• Has other concurrent medical or psychiatric conditions.
• Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
• Cohorts 3 to 5: Has an active autoimmune disease that required systemic treatment in
past 2 years (ie, with use of disease-modifying agents, corticosteroids, or
immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not
considered a form of systemic treatment.
• Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of
study drug(s), has history or evidence of interstitial lung disease (ILD) or
non-infectious pneumonitis.
• Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of
chemotherapy) in the neoadjuvant/adjuvant setting.
• Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval
>12 months between the last treatment administration and the date of recurrence is
required.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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
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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).
Obinutuzumab With or Without Umbralisib, Lenalidomide, or Combination Chemotherapy in Treating Patients With Relapsed or Refractory Grade I-IIIa Follicular Lymphoma
This phase II trial studies how well obinutuzumab with or without umbralisib, lenalidomide,
or combination chemotherapy work in treating patients with grade I-IIIa follicular lymphoma
that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy
with obinutuzumab, may induce changes in body's immune system and may interfere with the
ability of tumor cells to grow and spread. Umbralisib may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Biological therapies, such as
lenalidomide, use substances made from living organisms that may stimulate or suppress the
immune system in different ways and stop cancer cells from growing. Chemotherapy drugs, such
as cyclophosphamide, doxorubicin, vincristine, prednisone, and bendamustine, 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. It is not yet known whether giving
obinutuzumab with or without umbralisib, lenalidomide, or combination chemotherapy will work
better in treating patients with grade I-IIIa follicular lymphoma.
Vaishalee Kenkre, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03269669
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Inclusion Criteria:
• Patients must have follicular lymphoma (grade I, II or IIIa) confirmed at initial
diagnosis and at relapse with identifiable fludeoxyglucose F-18 (FDG) avid disease on
PET/CT; patients that have involvement with large cell lymphoma are not eligible
• Patients must have a whole body or limited whole body PET/CT scan performed within 42
days prior to registration
• Patients must have bone marrow biopsy performed within 42 days prior to registration
• Patients must have an indication for therapy as determined by the treating
investigator
• All disease must be assessed and documented on the S1608 FDG-PET/CT assessment form
• The intent is to enroll patients with follicular lymphoma (FL) relapsed within 2 years
of completing their first course of chemotherapy (CHOP or bendamustine based therapy)
+ anti-CD20 therapy. Patient is still eligible if he/she received radiation therapy or
anti-CD20 therapy prior to chemoimmunotherapy or if maintenance anti-CD20 therapy was
administered after chemoimmunotherapy
• Patients must have either failed to achieve a complete remission, or must have
relapsed within 2 years after completing CHOP or bendamustine-containing
chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from
the last dose of CHOP or bendamustine; relapsed patients must not have received
any intervening chemotherapy
• Patients must have received only 1 course of chemotherapy, containing at least 3
cycles of CHOP or bendamustine; (note that no minimum dose of bendamustine is
required)
• Patients who received any anti-CD20 antibody therapy prior to CHOP or
bendamustine are eligible
• Patients who additionally received any maintenance anti-CD-20 antibody therapy or
consolidative radioimmunotherapy within 2 years of the last dose of the CHOP or
bendamustine therapy are eligible
• Involved field or involved site radiation is not considered a line of therapy;
examples of eligible prior treatment regimens (note this list is not all
inclusive):
• 1st line rituximab treatment followed years later by bendamustine rituximab
• Bendamustine rituximab x 4 cycles
• 1st line rituximab treatment, 2nd line ibritumomab tiuxetan, followed by
bendamustine bortezomib rituximab x 6 cycles followed by rituximab
maintenance
• Bendamustine obinutuzumab x 3 cycles
• CHOP rituximab x 6 cycles followed by rituximab maintenance
• For all forms of systemic therapy, patients must have completed therapy at least 21
days prior to registration; patients must have completed any radioimmunotherapy at
least 84 days prior to registration; patients prior treatment related toxicities
(except alopecia) must have resolved to grade 1 or less prior to registration
• Patients must have tissue specimens collected prior to registration; patients must be
offered participation in biobanking of residual specimens; with patient consent,
residuals from the mandatory submission(s) will be banked for future research
• Patients must be >= 18 years of age
• All patients must have a Zubrod performance status of 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1,500/mcL within 28 days prior to registration
• Platelets >= 75,000/mcL within 28 days prior to registration
• Patients must have adequate renal function as documented by a calculated creatinine
clearance >= 60 mL/min, within 28 days prior to registration
• Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) (=< 5 x IULN if
secondary to lymphoma, Gilbert's syndrome, or medication related [e.g., indinavir,
tenofovir, atazanavir]) within 28 days prior to registration
• Direct bilirubin =< 1.5 x IULN (=< 5 x IULN if secondary to lymphoma) within 28 days
prior to registration
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x IULN (=<
5 x IULN secondary to lymphoma) within 28 days prior to registration
• Patients must have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan
within 42 days prior to registration with a cardiac ejection fraction >= 45%
• Patients with hepatitis B virus infection must have undetectable hepatitis B virus
(HBV) on suppressive therapy and no evidence of HBV-related hepatic damage; patients
with hepatitis C virus infection are eligible if complete eradication therapy has been
successfully completed, and there is no detectable hepatitis C virus (HVC) or related
hepatic damage; patients with known human immunodeficiency virus (HIV) infection are
eligible if they meet all of the following criteria in addition to the other protocol
eligibility criteria:
• Patient must have no history of acquired immune deficiency syndrome
(AIDS)-related complications, other than a history of low CD4+ T-cell count (<
200/mm^3) prior to initiation of combination antiretroviral therapy; on study
CD4+ T-cell count may not be informative due to leukemia and should not be used
as an exclusion criterion if low
• Patient must be healthy on the basis of HIV disease with high likelihood of near
normal life span were it not for the leukemia
• Patient must have serum HIV viral load of < 200 copies/mm^3
• Patient must be on combination antiretroviral therapy with minimal
pharmacokinetic interactions with study therapy and minimal overlapping clinical
toxicity with protocol therapy; (recommend a regimen of the integrase inhibitor
dolutegravir combined with either disoproxil fumarate/emtricitabine or
dolutegravir combined with tenofovir alafenamide/emtricitabine)
• Protease inhibitors and once daily formulations containing cobicistat are NOT
allowed due to potential pharmacokinetic interactions with leukemia therapy
• Stavudine and zidovudine (AZT) are NOT allowed because of overlapping toxicity
with protocol therapy
• Patients must be able and willing to receive prophylaxis with daily aspirin, low
molecular weight heparin, factor X inhibitors or warfarin if randomized to
lenalidomide; patients unable or unwilling to take any listed prophylaxis are NOT
eligible
• No second prior malignancy is allowed except for adequately treated basal (or squamous
cell) skin cancer, in situ cervical cancer or other cancer for which the patient has
been disease free for three years
• Patients must have a complete history and physical examination within 28 days prior to
registration
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24
hours prior to starting cycle 1 of lenalidomide; further, they must either commit to
complete abstinence (true abstinence is acceptable when this is in line with the
preferred and usual lifestyle of the subject; periodic abstinence [e.g., calendar,
ovulation, symptothermal or post ovulation methods] and withdrawal are not acceptable
methods of contraception) from heterosexual intercourse or begin TWO acceptable
methods of birth control: one highly effective method and one additional effective
method AT THE SAME TIME, at least 28 days before starting lenalidomide; while taking
lenalidomide, during dose interruptions, and for at least 28 days after the last dose
of lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to
use a latex condom during sexual contact with a FCBP, even if they have had a
successful vasectomy; a FCBP is a female who: 1) has achieved menarche at some point;
2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been
naturally postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had menses at
any time in the preceding 24 consecutive months); all patients must be counseled by a
trained counselor every 28 days about pregnancy precautions and risks of fetal
exposure; NOTE: patients not randomized to receive lenalidomide will not be required
to undergo serial pregnancy testing or lenalidomide counseling after registration
• Patients must have lactate dehydrogenase (LDH) and beta-2-microglobulin collected
within 28 days prior to registration
• Patients 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
Exclusion Criteria:
• Patients must not have clinical evidence of central nervous system involvement by
lymphoma since the proposed treatment strategies are not designed to address central
nervous system (CNS) involvement adequately; if performed, any laboratory or
radiographic tests performed to assess CNS involvement must be negative
• Patients must not have any prior treatment with any PI3K inhibitor, or lenalidomide
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
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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
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery
This randomized phase III trial studies how well radiation therapy works compared with
observation in treating patients with newly diagnosed grade II meningioma that has been
completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells
and shrink tumors.
Steven Howard, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT03180268
Show full eligibility criteria
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Inclusion Criteria:
• PRIOR TO STEP 1 REGISTRATION:
• The patient must have a newly diagnosed unifocal intracranial meningioma, gross
totally resected, and histologically confirmed as WHO grade II based upon pathology
findings at the enrolling institution; WHO grade will be assigned according to WHO
2016 criteria
• Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without
gross residual dural-based or extradural tumor; GTR must be confirmed both by modified
Simpson grade and by post-operative magnetic resonance imaging (MRI) findings
• Step 1 registration must occur within 180 days of the initial surgery; within this 180
day interval, a second surgery is permitted in order to achieve GTR, but even with a
second surgery, step 1 registration must occur within 180 days of the initial
resection
• For step 1 registration the operating neurosurgeon must provide the modified Simpson
grade
• GTR must be confirmed on post-operative imaging following the most recent surgery;
submission of both pre-operative and post-operative MRIs is required for patients; if
a second surgery is performed, submission of post-operative MRI is required and
pre-operative MRI is required only if obtained; all sequences obtained in the pre- and
post-operative MR imaging are to be submitted to National Radiology Group (NRG)
Oncology for study registration; imaging subsequent to enrollment must include pre and
post gadolinium contrast-enhanced three-dimensional spoiled gradient (SPGR),
magnetization-prepared rapid gradient echo (MP-RAGE), or turbo field echo (TFE) MRI
scan and an axial T2 fluid attenuated inversion recovery (FLAIR) sequence; to yield
acceptable image quality, the gadolinium contrast-enhanced three-dimensional SPGR,
MP-RAGE, or TFE axial MRI scan should use the smallest possible axial slice thickness
not exceeding 1.5 mm; the post-operative MRI must be completed within sufficient time
to permit step 1 registration within 180 days of the initial resection; these same
conditions apply in the setting of a second surgical procedure, although if a second
surgery is completed, step 1 registration must still occur with 180 days of initial
surgery; computed tomography (CT) imaging is not required, but may be obtained if
desired clinically, for instance to assess calcifications or hyperostosis
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• If the patient is a primary English speaker, the patient must participate in the NCF
and patient reported outcomes part of the study; if the patient is a primary French or
Spanish speaker, the patient must participate in the patient reported outcomes part of
the study
• NOTE: Central pathology review must occur between steps 1 and 2 of registration; once
appropriate pathology specimens are received, central pathology review will occur
within 15 days, and must confirm WHO grade II meningioma before the patient can
proceed to step 2 registration and randomization
• PRIOR TO STEP 2 REGISTRATION:
• Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central
pathology review prior to step 2 registration
• History/physical examination, including neurologic examination within 60 days prior to
step 2 registration
• Post-operative Zubrod performance status 0-1 within 60 days prior to step 2
registration
• If the patient is a woman is of childbearing potential, a serum pregnancy test,
obtained within 14 days prior to step 2 registration, must be negative, and, if
randomized to receive radiation therapy, the woman must agree to use contraception
Exclusion Criteria:
• Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple
meningiomas, hemangiopericytoma
• Definitive evidence of metastatic meningioma
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix,
melanoma in situ, or other non-invasive malignancies are permissible)
• Previous radiotherapy to the scalp, cranium, brain, or skull base and
radiation-induced meningiomas
• Major medical illnesses or psychiatric impairments, which in the investigators
opinion, will prevent administration or completion of the protocol therapy and/or
preclude informed consent; these include, but are not restricted to:
• Unstable angina and/or congestive heart failure requiring hospitalization at the
time of step 2 registration
• Transmural myocardial infarction within the last 6 months prior to step 2
registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of step 2 registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy at the time of step 2
registration
• Type II neurofibromatosis (NF2)
• Ailments entailing substantial increases in sensitivity and side effect risk from
radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human
immunodeficiency virus (HIV) with CD4 count < 200 cells/microliter); HIV testing
is not required for eligibility for this protocol, and known HIV positive
patients are eligible, provided they are under treatment with highly active
antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter
within 30 days prior to step 2 registration
• Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI
compatible implant or foreign body, etc) or receive gadolinium; note that
patients with severe claustrophobia are permitted on this study if they are
willing and able to undergo MRI with adequate sedation or anesthesia
• Pregnancy and/or nursing females
Brain and Nervous System, Brain/Central Nervous System, Grade II Meningioma, Intracranial Meningioma
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
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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
*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.