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.
67Cu-SARTATE™ Peptide Receptor Radionuclide Therapy Administered to Pediatric Patients With High-Risk, Relapsed, Refractory Neuroblastoma
The aim of this study is to evaluate the safety and efficacy of 67Cu-SARTATE in pediatric
patients with high-risk neuroblastoma.
Kenneth Desantes, M.D.
All
Not specified
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04023331
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Participant is able and willing to provide informed consent (≥18 years), or informed
consent is obtained by the parent or legal guardian for minor participants, with the
minor providing age appropriate assent, according to local law and regulations;
2. Life expectancy ≥ 12 weeks;
3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has
relapsed or progressed to high-risk, with failure to achieve complete response with
standard therapy (defined as at least 4 cycles of aggressive multi-drug induction
chemotherapy with or without radiation and surgery, or according to a standard
high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to
receive standard treatment OR who are intolerant to standard treatment;
4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the
Investigator or treating Sub-Investigator;
5. Adequate liver function as defined by the following laboratory values obtained within
28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN);
6. Adequate renal function;
7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet
count > 50 x 10 9/L; Total bilirubin <1.5 x ULN;
8. Karnofsky or Lansky performance status ≥50;
9. All participants must have a hematopoietic stem cell product available (minimum CD34+
cell dose is ≥2 x 10 6 cells/kg);
10. Sexually active participants of reproductive potential must practice an effective
method of birth control while participating on this study, to avoid possible damage to
the fetus. Abstinence is considered acceptable;
11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than
that of the liver in order to move on to the therapy phase of the study.
Exclusion Criteria:
1. Participants with disease of any major organ system that would compromise their
ability to tolerate therapy, as deemed by the Investigator or treating
Sub-Investigator;
2. Any other active malignancy, or a history of prior malignancy within the past 3 years;
3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance,
oxygen requirement, clinically significant cardiac dysfunction;
4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or
radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE;
5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the
administration of 64Cu-SARTATE;
6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney
within 12 months prior to the administration of 64Cu-SARTATE;
7. Administration of any investigational agents within 21 days prior to administration of
64Cu-SARTATE;
8. Treatment with long acting somatostatin analogues (administered within 28 days prior
to the administration of 64Cu-SARTATE), or short acting somatostatin analogues
(administered within 24 hours prior to the administration of 64Cu-SARTATE);
9. Known sensitivity or allergy to somatostatin analogues;
10. Previous peptide receptor radionuclide therapy (PRRT);
11. Female participants who are pregnant or lactating;
12. Participants who are on hemodialysis;
13. QTc interval ≥ 0.45 seconds as measured by Screening ECG;
14. Participants with uncontrolled infection(s);
15. Any medical condition which the Investigator feels may interfere with the procedures
or evaluations of the study;
16. Participants 12 months and younger will be excluded from cohorts where the planned
single or cumulative administered activity is modelled to deliver a radiation dose to
the marrow that exceeds 2 Gy.
Neuroblastoma, Relapsed Neuroblastoma, Refractory Neuroblastoma, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
A Study to Compare Two Surgical Procedures in Individuals With BRCA1 Mutations to Assess Reduced Risk of Ovarian Cancer (SOROCk)
This clinical trial studies how well two surgical procedures (bilateral salpingectomy and
bilateral salpingo-oophorectomy) work in reducing the risk of ovarian cancer for individuals
with BRCA1 mutations. Bilateral salpingectomy involves the surgical removal of fallopian
tubes, and bilateral salpingo-oophorectomy involves the surgical removal of both the
fallopian tubes and ovaries. This study may help doctors determine if the two surgical
procedures are nearly the same for ovarian cancer risk reduction for women with BRCA1
mutations.
Lisa Barroilhet, MD
Female
35 Years to 50 Years old
N/A
This study is NOT accepting healthy volunteers
NCT04251052
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Individuals 35-50 years of age, inclusive
• Patients who are undergoing risk-reducing salpingo-oophorectomy (RRSO) (for the BSO
arm) and patients who have declined or elected to defer BSO after proper counselling
to clearly explain the standard of care for BRCA1 mutation carriers and are undergoing
salpingectomy (for the BLS arm with delayed oophorectomy arm). Concurrently planned
hysterectomy with either arm is permitted
• At least one intact ovary and fallopian tube is in situ at the time of counseling and
consent. Prior hysterectomy is allowed provided it did not include bilateral
salpingectomy. Prior tubal ligation is allowed if one intact ovary and fallopian tube
(with fimbria not removed) are present
• Positive Clinical Laboratory Improvement Act (CLIA)-approved test results for
pathogenic or likely pathogenic germline BRCA1 mutation in the patient. Documentation
of the result is required
• Patients may be premenopausal or menopausal
• Transvaginal ultrasound (TVUS) and CA-125 within 180 days of registration
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
• Individuals who are currently pregnant or plan to become pregnant in the future
through assisted reproductive technologies and who have received proper counseling are
eligible. Individuals who are currently pregnant and plan bilateral salpingectomy at
the time of a planned cesarean section are eligible. Patients must understand that
they will not be able to become pregnant naturally in the future
Exclusion Criteria:
• Individuals with a history of any prior cancer who have received chemotherapy within
the past 30 days or radiotherapy to abdomen or pelvis at any prior time
• Prior history of ovarian cancer, including low malignant potential neoplasms (LMP),
primary peritoneal carcinoma, or fallopian tube carcinoma
• Patients medically unfit for the planned surgical procedure
• Patients with abnormal screening tests (TVUS, CA-125) suspicious for occult or gross
pelvic malignancy or neoplasm within the past 180 days
• An abnormal TVUS is defined as morphologic or structural variations suspicious
for ovarian malignancy or complex cystic lesions (simple cysts < 5 cm in maximal
diameter are not exclusionary)
• An abnormal CA-125 is defined as a level > 50 U/ml in premenopausal individuals
if they are not current users of oral contraceptives; an abnormal CA-125 is
defined as a level > 40 U/ml for premenopausal individuals who are current users
of oral contraceptives. An abnormal CA-125 is defined as a level > 35 U/ml in
postmenopausal individuals.
A Study to Evaluate the Safety and Tolerability of AB680 in Participants With Gastrointestinal Malignancies (ARC-8)
This is a Phase 1, open-label, dose-escalation, and dose-expansion, with a gated
randomization portion, study to evaluate the safety, tolerability, pharmacokinetic,
pharmacodynamic and clinical activity of AB680 in combination with Zimberelimab (AB122),
nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04104672
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Capable of giving signed informed consent
• Male or female participants ≥ 18 years of age at the time of screening
• Negative serum pregnancy test at screening and prior to dosing on Cycle 1 Day 1;
negative serum or urine pregnancy test on the first day of each subsequent treatment
period
• Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma
• Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted
therapy for metastatic disease
• Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for
pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was
completed at least 6 months prior to study enrollment. Prior adjuvant therapy may
include Nab- paclitaxel or gemcitabine
• Participants initially diagnosed with locally advanced pancreatic cancer who have
undergone chemotherapy then resection and had no evidence of disease are eligible
if relapse of metastatic disease has occurred and if the last dose of
chemotherapy was received more than 6 months before study entry
• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1. The measurable lesion must be outside of a radiation field if
the participant received prior radiation
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Confirmation that an archival tissue sample is available; if not, a new biopsy of a
tumor must be obtained
• Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed
topical corticosteroids (doses > 10 mg/day prednisone or equivalent) must be
discontinued at least 2 weeks (14 days) before investigational product administration.
Physiologic doses of corticosteroids (≤ 10 mg/day of prednisone or its equivalent) or
short pulses of corticosteroids (≤ 3 days) may be permitted
• Prior surgery that required general anesthesia or other major surgery as defined by
the Investigator must be completed at least 4 weeks before investigational product
administration
• Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or
hepatitis C qualitative ribonucleic acid [RNA; qualitative]), and human
immunodeficiency virus (HIV)-1 and HIV-2 antibody at screening
• Adequate organ and marrow function
Exclusion Criteria:
• Use of any live attenuated vaccines against infectious diseases (eg, influenza,
varicella) within 4 weeks (28 days) of initiation of investigational product
• Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will
make the administration of investigational product hazardous (eg, interstitial lung
disease, active infections requiring antibiotics, recent hospitalization with
unresolved symptoms
• Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
• Any active autoimmune disease or a documented history of autoimmune disease or history
of a syndrome that required systemic steroids or immunosuppressive medications, except
for vitiligo or resolved childhood asthma/atopy. Participants with asthma who require
intermittent use of bronchodilators (such as albuterol) will not be excluded from this
study
• Prior malignancy active within the previous year except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate
cancer
Evaluation of PSMA in HER2- AR+ Metastatic Breast Cancer
The purpose of this research is to determine the expression of prostate specific membrane
antigen (PSMA) in human epidermal growth factor receptor 2 (HER2)-negative, androgen receptor
(AR)-positive metastatic breast cancer, and to determine its role in resistance to the
anti-androgen, bicalutamide. The investigators hypothesize that PSMA expression will
correlate with resistance to anti-androgen therapies, as has been documented in prostate
cancer, and this can be used to select patients most likely to benefit from these therapies
in future clinical trials. 15 people with HER2-negative, AR-positive metastatic breast cancer
will be enrolled and be on study for about 3 days.
Steve Cho
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04573231
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients diagnosed with metastatic HER2-negative breast cancer AR expression of ≥ 10%
Exclusion Criteria:
• Other (non-breast) known active malignancy. Participants with previously treated
cancers which are in remission or have no evidence of disease are eligible.
• Unable to lie flat during or tolerate PET/CT
• Participants with any medical condition or other circumstances that, in the opinion of
the investigator, compromise the safety or compliance of the subject to produce
reliable data or completing the study
• Women of childbearing potential must not be pregnant or breast feeding (pregnancy test
negative within 7 days prior to PET/CT
Breast Cancer, HER2-negative Breast Cancer, Metastatic Breast Cancer, Breast
Early-Line Anti-EGFR Therapy to Facilitate Retreatment for Select Patients With mCRC
The study will use previously established doses of panitumumab or cetuximab in the metastatic
setting for the treatment of unresectable colorectal cancer (CRC). It is designed to
investigate an alternative treatment strategy to maximize the benefit to inhibition of
epidermal growth factor receptor (EGFR) for a highly selected patient population. It will
enroll 71 participants with left-sided, unresectable metastatic CRC. Participants will be on
study up to 5 years.
Dustin Deming, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04587128
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Written informed consent and HIPAA authorization for release of personal health
information
• As determined by the enrolling physician or protocol designee, ability of the
participant to understand and comply with study procedures for the entire length of
the study
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
• Have a diagnosis of histologically confirmed metastatic colorectal cancer with primary
tumor located beyond the splenic flexure. Histologic confirmation of a colorectal
primary tumor is acceptable if accompanied by radiographic evidence of metastatic
disease.
• For Cohort A: Participants must enroll for study treatment in the first or
second-line metastatic setting. Participants may receive 1 month of standard
chemotherapy in the metastatic setting and still be eligible to initiate protocol
therapy in the first-line setting. Adjuvant or neoadjuvant therapy does not count
as a line of therapy even if given in the setting of metastatic disease
(oligometastatic), unless disease recurrence was noted within 6 months of
completing the last dose of the adjuvant or neoadjuvant therapy.
• For Cohort B: Participants must have had at least stable disease (per treating
physician) on a prior EGFR inhibitor containing regimen and it must be at least 4
months since the prior anti-EGFR inhibitor treatment was completed. Participants
previously enrolled in Cohort A can later enroll in Cohort B should the
eligibility criteria be met.
• For Cohort C: Subjects must have had prior FOLFOX +/- VEGF inhibitor with no
prior use of irinotecan or anti-EGFRi. If patients had prior FOLFOX and were
treated on cohort A (of this study) they can cross-over to cohort C if other
eligibility criteria are met at the time of cross-over.
• Evaluable disease according to RECIST v1.1. Participants do not have to have
measureable disease.
• Participants with prior brain metastasis may be considered if they have completed
their treatment for brain metastasis at least 4 weeks prior to study registration,
have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
• Demonstrate adequate organ function; all screening labs to be obtained within 7 days
prior to registration. Note minimum platelet requirement differs between Cohort A and
B.
• Absolute Neutrophil Count (ANC) ≥ 1,000 / mcL
• Platelets ≥ 50,000 / mcL (Cohort A); ≥ 50,000 mcL (Cohort B receiving only
EGFRi); ≥75,000 / mcL (cohort B receiving irinotecan and EGFRi; and cohort C)
• Serum creatinine OR measured or calculated creatinine clearance (GFR can also be
used in place of creatinine or CrCl) ≤ 2.0 X upper limit of normal (ULN) OR ≥ 60
mL/min for subject with creatinine levels > 2.0 X institutional ULN
• Bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for subjects with bilirubin
levels >1.5 x ULN
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 5 × ULN
• Albumin ≥ 2.5 mg/dL
• Females of childbearing potential must have a negative serum pregnancy test within 7
days of registration and not be breastfeeding. 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 must be willing to abstain from
heterosexual activity or to use 2 forms of effective methods of contraception from the
time of informed consent until 120 days after treatment discontinuation. The two
contraception methods can be comprised of two barrier methods, or a barrier method
plus a hormonal method.
• Tumor must be mismatch repair (MMR) proficient as determined by microsatellite
instability or immunohistochemistry for MMR proteins
• Microsatellite instability (MSI) testing must be MSI-stable or MSI-low.
• Or IHC for MMR proteins must demonstrate intact MMR proteins.
• Baseline (prior to any anti-EGFR treatment) tumor molecular profiling with no
pathologic variants in KRAS or NRAS or BRAF V600 mutations. If additional molecular
profiling is completed (tissue or blood based testing) after receiving treatment for
colon cancer and variants in KRAS or NRAS are found, those patients will be considered
eligible for this study. Patients with BRAF V600 mutations are not eligible.
• Participants must not have known additional malignancy that is requiring systemic
treatment. Participants taking hormonal treatments for breast or prostate cancer are
still eligible.
• No major surgery within prior 2 weeks of treatment initiation (4 weeks if will be
receiving bevacizumab).
• Urine protein less than 100 mg/dL if planning to receive bevacizumab.
• Blood pressure <160/90 if planning to receive bevacizumab.
• No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to panitumumab or cetuximab, including known severe
hypersensitivity reactions to monoclonal antibodies. No history of allergic reactions
to 5-Fluorouracil, irinotecan, leucovorin or bevacizumab if the participant will be
receiving that agent in this study.
• Participants must have no metastatic cancer lesions greater than 3.5cm in diameter.
Any number of metastatic lesions will be allowed.
Metastatic Colorectal Cancer, Colon, Rectum, Colon and Rectum
The primary purpose of this study is to discover new disease genes for rare Mendelian
disorders and its secondary purpose include diagnosing people with rare genetic disorders
that have not been previously diagnosed through conventional clinical means, learning more
about the pathobiology of genetic disorders, and developing novel diagnostic technologies and
analytics. 500 participants with undiagnosed and suspected genetic disorders will be
recruited over approximately 5 years time.
Stephen Meyn
All
up to 100 Years old
NA
This study is NOT accepting healthy volunteers
NCT04586075
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• The applicant has a condition that remains undiagnosed despite thorough evaluation by
healthcare providers (including clinical genetic testing).
• The applicant has at least one objective finding that is likely to have an
identifiable genetic etiology.
• The applicant likely has a currently undescribed/new genetic condition or a known
genetic condition associated with a novel gene.
• The applicant/legal guardian agrees to the collection, storage and recurrent sharing
of coded information and biomaterials for research and diagnostic purposes both within
and outside of the University of Wisconsin-Undiagnosed Diseases Program (UW-UDP)
• The applicant/legal guardian agrees to receive secondary findings from genetic
testing.
• The applicant/legal guardian has sufficient proficiency in English to understand the
consent.
Exclusion Criteria:
• The applicant already has a diagnosis that explains the objective findings.
• A specific diagnosis is suspected and a standard clinical workup performed by the
referring/primary care provider would be appropriate.
• The UW-UDP is unlikely to improve on the comprehensive workup the applicant has
already received.
• The applicant's symptoms are likely multifactorial or due to a non-genetic cause.
Rare Diseases, Genetic Disease, Undiagnosed Disease, Other specified congenital malformation syndromes affecting multiple systems, Other
A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)
The primary purpose of this study is to determine the antitumor activity of enfortumab
vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1.
This study will also assess other measures of antitumor activity; overall survival (OS); as
well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab
vedotin + pembrolizumab in cohort 9.
Justine Bruce, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04225117
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Subject is considered an adult according to local regulation at the time of signing
the informed consent form (ICF).
• Subject has measurable disease by RECIST Version 1.1.
• Subject has accessible archival tumor tissue from either the primary tumor or a
metastatic site, for which source and availability have been confirmed prior to study
treatment. If no archival tumor tissue is available, the subject will have a biopsy to
obtain tumor tissue prior to study treatment. If the subject is unable to undergo a
biopsy due to safety concerns, enrollment into the study must be discussed with the
medical monitor.
• For cohort 9 only: Subject should submit archival or fresh tumor tissue sample for
programmed cell death-ligand 1 (PD-L1) central testing during screening if no local
PD-L1 test result is available. Central test result for PD-L1 will be required prior
to subject enrollment. For cohort 9 subjects with local PD-L1 test result confirming
CPS ≥ 1, archival or fresh tissue sample for exploratory analysis should be submitted
within 5 days of enrollment.
• Subject has ECOG performance status of 0 or 1.
• Subject has the following baseline laboratory data. If a subject has received a recent
blood transfusion, the hematology tests must be obtained ≥ 28 days after any blood
transfusion.
• absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• platelet count ≥ 100 × 10^9/L
• hemoglobin ≥ 9 g/dL
• serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for
subjects with Gilbert's disease
• creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards
or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can
also be used instead of CrCl).
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Subject agrees not to participate in another interventional study while receiving
study treatment in the present study.
• Additional contraceptive requirements exist for male and female subjects.
Disease Specific
Inclusion Criteria:
• Evidence of progression on or after the last regimen received.
• Locally advanced or metastatic disease that is not amenable to curative intent
treatment.
Cohort 1: HR+/HER2- breast cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor
[ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast
cancers and are not considered a candidate for further hormonal therapy. Subject will
be considered HR+ if biopsies show ≥ 1% expression of ER or PR as per current American
Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. No limit applies to
endocrine therapies. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a
line of cytotoxic therapy.
• Subject has progressed, relapsed, or discontinued for toxicity during or after
receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent
kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required.
Cohort 2: triple negative breast cancer (TNBC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal
TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1%
expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either
0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not
amplified) as per current ASCO/CAP guidelines.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or
incurable, locally advanced or metastatic setting.
• Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will
count as a prior cytotoxic regimen if disease recurrence occurred during or
within 6 months of completing the regimen.
• Subject has progressed, relapsed, or discontinued for toxicity during or after at
least 1 prior standard of care cytotoxic regimen in the incurable, unresectable
locally advanced or metastatic setting, and has not received > 2 prior lines of
cytotoxic therapy in the locally advanced or metastatic setting. Poly(ADP-ribose)
polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
• Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1)
or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or
PD-L1 expression and local treatment guidelines and has progressed or discontinued
treatment due to toxicity, or therapy is contraindicated for subject.
Cohort 3: squamous non-small cell lung cancer (NSCLC)
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically or cytologically-confirmed squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma
kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations
are eligible if treated with mutation targeted therapy and have progressed,
relapsed, or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression had occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 4: non-squamous non-small cell lung cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed non-squamous NSCLC.
• Subjects with mixed histology NSCLC are eligible provided there is not any
component of neuroendocrine histology.
• Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are
eligible if treated with mutation targeted therapy and have progressed, relapsed,
or discontinued treatment due to toxicity.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
1. Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months of completion.
2. Maintenance therapy does not constitute a new chemotherapy regimen provided there
was no progression after the initial platinum-based regimen.
3. Changing chemotherapy agents during platinum-based treatment for the management
of toxicities does not constitute a new chemotherapy regimen provided no
progression has occurred while on the initial therapy.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 5: second-line or later head and neck cancer
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed head and neck cancer.
• Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors
and/or parotid gland tumors are not eligible for Cohort 5.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Subjects with locally advanced disease who previously received curative intent
treatment with platinum-based standard of care regimen in the adjuvant or
neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible
if they have progressed or relapsed within 6 months after completion.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohorts 6, 7 and 8: gastric or gastroesophageal junction (GEJ) or esophageal adenocarcinoma
• Subject has evidence of radiographic progression on or after the last regimen
received.
• Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal
cancer.
• Subject has locally advanced or metastatic disease that is not amenable to curative
intent treatment.
• Subject has progressed, relapsed, or discontinued due to toxicity after 1
platinum-based standard of care regimen for locally advanced or metastatic disease,
and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally
advanced or metastatic setting.
• Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if
relapsed or progressed ≤ 6 months after completion.
• Subject must have received a HER2 directed therapy if known to have HER2 positive
cancer.
• Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's
tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed,
relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for
subject.
Cohort 9: 1L HNSCC
• Subject has histologically- or cytologically-confirmed head and neck squamous cell
carcinoma.
a. Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and
larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or
parotid gland tumors are not eligible for Cohort 9.
• Subject has recurrent or metastatic disease that is incurable by local therapies.
• Subject's tumor sample has PD-L1 combined positive score (CPS) of ≥ 1 as determined by
local or central IHC testing.
• Subject has had no prior systemic therapy administered with the exception of systemic
therapy completed > 6 months prior if given as part of multimodal treatment for
locally advanced disease. Subjects who have received a PD-1 or PD-L1 inhibitor in the
curative setting are eligible if it has been at least 12 months since last dose of the
anti PD-L1 agent.
• Subject has ANC ≥ 1.5 × 10^9/L.
• International normalized ratio (INR) OR prothrombin time (PT) and activated partial
thromboplastin (aPTT) both ≤ 1.5 × ULN unless subject is receiving anticoagulant
therapy as long as PT or aPTT is within the therapeutic range of intended use of
anticoagulants. PTT may be used if local lab is unable to perform aPTT.
• For subjects with oropharynx tumors, subject has results from testing of HPV status by
p16 testing.
Exclusion Criteria:
For All Cohorts:
• Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
• Subject has active central nervous system (CNS) metastases. Subjects with treated CNS
metastases are permitted on study if all the following are true:
• CNS metastases have been clinically stable for ≥ 6 weeks prior to screening
• If requiring steroid treatment for CNS metastases, the subject is on a stable
dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks
• Baseline imaging scans show no evidence of new or enlarged brain metastasis
• Subject does not have leptomeningeal disease
• Subject has ongoing clinically significant toxicity (Grade 2 or higher with the
exception of alopecia) associated with prior treatment (including systemic therapy,
radiotherapy or surgery).
• Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or
panhypopituitarism are excluded. Subjects with ongoing immunotherapy-related colitis,
uveitis, myocarditis or pneumonitis, or subjects with other immunotherapy-related AEs
requiring high doses of steroids (> 20 mg/day of prednisone or equivalent), are
excluded. Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or
panhypopituitarism may be enrolled when well maintained/controlled on a stable dose of
hormone replacement therapy (if indicated).
• Subject has a history of uncontrolled diabetes mellitus within 3 months before the
first dose of study treatment. Uncontrolled diabetes (within 3 months before first
dose) is defined as hemoglobin A1c (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with
associated diabetes symptoms (polyuria or polydipsia) that are not otherwise
explained. The lowest HbA1c during the screening period will be used to determine
eligibility.
• Subject has prior treatment with enfortumab vedotin or other monomethyl auristatin E
(MMAE) based antibody-drug conjugates (ADCs).
• Subject has a second malignancy diagnosed within 3 years before first dose of study
drug, or any evidence of residual disease from a previously diagnosed malignancy.
Subjects with non-melanoma skin cancer, localized prostate cancer treated with
curative intent with no evidence of progression, low-risk or very low-risk (per
standard guidelines) localized prostate cancer under active surveillance/watchful
waiting without intent to treat, or carcinoma in situ of any type (if complete
resection was performed) are allowed.
• Subject is currently receiving systemic antimicrobial treatment for viral, bacterial,
or fungal infection at the time of first dose of study treatment. Routine
antimicrobial prophylaxis is permitted.
• Subject has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg]
reactive) or active hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is
detected).
• Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or
2).
• Subject has documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction or cardiac symptoms
(including congestive heart failure) consistent with New York Heart Association Class
III-IV within 6 months prior to the first dose of study drug.
• Subject has major surgery within 4 weeks prior to first dose of study drug.
• Subject had radiotherapy, chemotherapy, biologics, investigational agents, and/or
antitumor treatment with immunotherapy that is not completed 2 weeks prior to first
dose of study drug.
• Subject has known hypersensitivity to enfortumab vedotin or to any excipient contained
in the drug formulation of enfortumab vedotin (including histidine, trehalose
dihydrate and polysorbate 20) OR subject has known hypersensitivity to
biopharmaceutical produced in Chinese hamster ovary cells.
• Subject has known active keratitis or corneal ulcerations. Subject with superficial
punctate keratitis is allowed if the disorder is being adequately treated.
• Subject has any condition which makes the subject unsuitable for study participation.
Cohort 9: 1L HNSCC
• Had PD within 6 months of completion of curatively intended systemic treatment for
locoregionally advanced HNSCC.
• Has had an allogeneic tissue/solid organ transplant. Has severe hypersensitivity
(≥grade 3) to pembrolizumab and/or any of its excipients.
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that
required steroids or has current pneumonitis / interstitial lung disease.
• Has a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease
(e.g. tumor bleeding, uncontrolled tumor pain) in the opinion of the treating
investigator.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
1. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed.
2. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered
standard of care.
3. Subjects with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or
resolved childhood asthma/atopy will not be excluded.
4. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or
local steroid injections will not be excluded.
5. Subjects with hypothyroidism that is stable with hormone replacement or Sjögren's
syndrome will not be excluded.
• Has an active infection requiring systemic therapy.
• Has received prior therapy with an anti-PD-1 or anti-PD-L1 agent in the
recurrent/metastatic setting. If anti-PD-1 or anti-PD-L1 agent was given as part of
curative intent therapy, it must be at least 1 year since last dose.
• Has received a live vaccine within 30 days of planned start of study therapy. Examples
of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette
Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally
killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,
FluMist®) are live attenuated vaccines and are not allowed.
• Subject has active tuberculosis
Locally Advanced or Metastatic Malignant Solid Tumors, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Larynx, Lung, Breast, Eye and Orbit, Head and Neck, Melanoma/Skin cancer
A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer
This phase I trial studies the side effects and best dose of peposertib when given together
with pegylated liposomal doxorubicin hydrochloride in treating patients with high or low
grade ovarian cancer that has come back after a period of improvement (recurrent). Peposertib
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving peposertib and pegylated
liposomal doxorubicin hydrochloride may work better in treating patients with ovarian cancer
compared to pegylated liposomal doxorubicin hydrochloride alone.
Lisa Barroilhet, MD
Female
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT04092270
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian,
fallopian tube or primary peritoneal cancer are eligible. This includes, but is not
limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/
high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous
adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed
epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not
otherwise specified
• NOTE: Patients who have evidence of DDR deficiency /HRD are eligible if they are
at the point in their disease course where they are appropriate candidates for
single agent Doxil
• EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low
grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)
• Patients accrued to the LGSOC cohort will have recurrent or persistent low grade
serous ovarian cancer or grade 1 serous ovarian cancer
• Patients accrued to the HGSOC cohort will have recurrent or persistent high grade
serous ovarian cancer
• Patients must have measurable disease by defined Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria
• Prior therapy:
• Patients must have received at least one prior line of platinum-based
chemotherapy
• Patients can have received an unlimited number of additional lines of
chemotherapy, targeted therapy, biologic therapy, or hormonal therapy
• Any prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted therapy, immunotherapy, or hormonal therapy must be
discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest)
prior to study treatment initiation
• Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in
patients < 18 years of age, children are excluded from this study, but will be
eligible for future pediatric trials
• Patients with platinum-sensitive ovarian cancer are eligible for only the dose
expansion phase if their provider feels that PLD would be an appropriate treatment
option for them. Patients with platinum-sensitive ovarian cancer should also be
offered any higher priority studies for which they are potentially eligible and/or
platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients must have a cardiac ejection fraction >= the institutional lower limit of
normal (LLN)
• Hemoglobin >= 9 g/dL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN
• Alkaline phosphatase =< 2.5 x institutional ULN
• Creatinine clearance > 30 ml/min
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression. The
patient must be off steroids and clinically stable
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required
• The effects of peposertib (M3814) and liposomal doxorubicin on the developing
human fetus are unknown and there is the potential for teratogenic or
abortifacient effects. For this reason, women and men of child-bearing potential
must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study treatment,
and for 6 months after completion of peposertib (M3814) administration. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately. Because there is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with peposertib (M3814),
breastfeeding should be discontinued if the mother is treated with peposertib
(M3814)
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
• Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36
months prior to registration must be available for submission for deoxyribonucleic
acid (DNA)/ribonucleic acid (RNA) analysis
Exclusion Criteria:
• Patients are excluded from the dose-escalation phase of the study if they are eligible
for any available therapies known to confer clinical benefit
• Inability to swallow and/or absorb oral medication (patients with a drainage peg are
ineligible)
• Patients may not have received prior anthracyclines (doxorubicin or pegylated
liposomal doxorubicin) for treatment of their ovarian cancer
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia, thyroid
dysfunction, or neuropathy
• Patients who are receiving any other investigational agents within 28 days prior to
start of treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to peposertib (M3814) or pegylated liposomal doxorubicin
• Patients who cannot discontinue concomitant medications or herbal supplements that
potentially interact with peposertib (M3814)
• The following categories of medications and herbal supplements must be
discontinued prior to starting study treatment:
• Strong inducers/inhibitors of CYP3A4/5, CYP2C9, and CYP2C19
• Substrates of CYP3A4/5, CYP1A2, and CYP2B6 with a narrow therapeutic index
• Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6 and substrates of
P-gp, BCRP, OCT1, OATP1B1, and OATP1B3 with a narrow therapeutic index. Close
monitoring is advised
• Because the lists of these agents are constantly changing, it is important to
regularly consult a frequently-updated medical reference. As part of the
enrollment/informed consent procedures, the patient will be counseled on the risk
of interactions with other agents, and what to do if new medications need to be
prescribed or if the patient is considering a new over-the-counter medicine or
herbal product. Patient Drug Interactions Handout and Wallet Card) should be
provided to patients
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients
may confer with the study doctor to determine if such medications can be discontinued.
These must be discontinued >= 5 days prior to study treatment. Patients do not need to
discontinue calcium carbonate
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
are excluded
• Patients who have received a live attenuated vaccine within 30 days of dosing with
peposertib (M3814)
• Patients with uncontrolled intercurrent illness, including but not limited to ongoing
or active infection
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• Pregnant women are excluded from this study because peposertib (M3814) is DNA-PK
inhibitor agent with the potential for teratogenic or abortifacient effects. Because
there is an unknown but potential risk for adverse events in nursing infants secondary
to treatment of the mother with peposertib (M3814), breastfeeding should be
discontinued if the mother is treated with peposertib (M3814). These potential risks
may also apply to other agents used in this study
• Patients with significant (uncontrolled) cardiac conduction abnormalities are excluded
Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
The purpose of this research is assess imaging and identification of soft plaque that
undergoes large deformations or strain will identify plaque vulnerable to rupture which could
lead to 'silent strokes'. Validation of current study results with MRI will foster use of
real-time ultrasound (US) strain imaging and strain indices as a screening tool for
identifying normal human participants susceptible to increased vascular aging and developing
plaque prone to rupture or micro-embolization.
Current research will evaluate Lagrangian carotid strain imaging (LCSI) for prediction of
vascular health on volunteers. In this study, investigators will evaluate age-related strain
variations (due to plaque deposition) in the carotid artery, establishing groundwork that
will help identify typical and atypical values for these indices. Investigator's hypothesis
is that plaques with higher strain indices (softer plaques) are more prone to rupture than
plaques with lower strain indices (stiffer) plaques, thus requiring intervention. Clinical
criteria for treatment has focused primarily on the degree of stenosis. Long-term objectives
are to provide non-invasive methods for screening participants at risk for vascular aging or
plaque rupture in asymptomatic participants, expanding upon current criteria for risk
assessments based on focal transient ischemic attack (TIA) or strokes. Variations in vessel
strain have been associated with, or are precursors to, plaque deposition, vascular aging, or
cerebrovascular diseases. Increased arterial strain and pressure changes have been linked to
brain aging using magnetic resonance imaging (MRI) based vascular indices, and memory
deficits commonly linked to Alzheimer dementia. Stiffening and thickening of the arterial
walls have also been associated with cerebrovascular disease. Investigators hypothesize that
strain indices as vascular biomarkers can be utilized for screening possible 'vulnerable
participants' validated with MRI, with the potential ability to improve endothelial function
and reverse vascular aging. Strain indices may enable differentiating study participants with
vascular cognitive impairment (VCI) from other dementias. Cognitive testing is unable to make
this differentiation.
Tomy Varghese, Ph.D.
All
18 Years and over
N/A
This study is also accepting healthy volunteers
NCT04632485
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
Aim 1 (Ultrasound (US) only):
• Adults at least 18 years
• Are able to provide written informed consent on their own behalf
Aim 2 (US and MRI):
• Participation in the US study (Aim 1)
• Determined by presence of hypoechogenic or echolucent lipid-rich soft plaque during
initial ultrasound imaging session
• Adults willing to participate over 5 years
Exclusion Criteria:
Aim 1 (US only)
• Women that are currently pregnant
• Inability to cooperate with the ultrasound study, in particular those unable to sit
without gross movement for the duration the ultrasound study (estimated at 60-90
minutes)
• Open wounds or sores in the anterior neck
• History of cardiac disease, stroke or TIA
• History of statin medication
• History of hypertension medications
Aim 2 (US and MRI):
• Women that are currently pregnant
• Inability to cooperate with the ultrasound study, in particular those unable to sit
without gross movement for the duration the ultrasound study (estimated at 60-90
minutes)
• Patients that require intravenous (IV) conscious sedation for imaging are not
eligible; patients requiring mild, oral anxiolytics for research imaging will be
allowed to participate as long as:
• The participants has their own prescription for the medication;
• The informed consent process is conducted prior to the self-administration of this
medication; and,
• The participant comes to the research visit with a driver
• Contraindications to MR
• Unable to lie in the MRI scanner for 45-60 minutes
• Patients with a contraindication to gadolinium based contrast agents, including
allergy or impaired renal function (per University of Wisconsin Health Guidelines)
Healthy, Carotid Artery Diseases, Healthy Volunteers, Other
This study is to prospectively compare the effectiveness and safety of the two types of
arteriovenous access placement (fistula or graft) in older adults with end stage kidney
disease and multiple chronic conditions
Ali Gardezi
All
60 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04646226
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Age 60 years or older
• End-stage kidney disease on hemodialysis via a central venous catheter
• Hemodialysis is the long-term modality of treatment for end-stage kidney disease
• Central venous catheter is the sole vascular access used for hemodialysis at the time
of referral for arteriovenous access creation
• Referred by patient's nephrologist for placement of arteriovenous access
• At least one of the following comorbid conditions: cardiovascular disease, peripheral
vascular disease, and/or diabetes mellitus
• Medically and surgically eligible to undergo surgical placement of an arteriovenous
access, deemed by the treating healthcare providers
• Native vasculature deemed preoperatively to be suitable for surgical creation of
either type of arteriovenous access (arteriovenous fistula or arteriovenous graft) in
the opinion of the surgeon
• Patient agreed to study participation and signed the informed consent
Exclusion Criteria:
• Severe cardiac disease defined as presence of either of the following three
conditions: congestive heart failure with ejection fraction ≤ 20%, heart transplant,
or ventricular assist device
• Known or suspected central vein stenosis or vascular obstruction on the side of
planned study access creation, unless corrected prior to randomization
• Planned arteriovenous fistula creation by means other than suture or vascular
anastomotic clips (e.g. endovascular surgery or other anastomotic creation devices)
• Anticipated kidney transplant within 12 months
• Anticipated conversion to peritoneal dialysis within 12 months
• Anticipated transfer of nephrology care to a clinic outside the study participating
centers within 12 months
• Anticipated non-compliance with medical care based on physician judgment
• A condition in which, in the opinion of the site PI renders the patient not a good
candidate for study participation.
Antecedent Metabolic Health and Metformin Aging Study (ANTHEM)
Aging is the number one risk factor for the majority of chronic diseases. There are no
pharmaceutical treatments to slow aging and prolong healthspan. The anti-diabetic drug
metformin is considered a likely pharmaceutical candidate to slow aging. In this study, the
investigators hypothesize that metformin treatment in subjects free of type 2 diabetes will
improve insulin sensitivity and glucoregulation in insulin resistant individuals, but will
decrease insulin sensitivity and glucoregulation in insulin sensitive subjects. Further, the
investigators hypothesize that long-term metformin treatment will remodel mitochondria in a
way that decreases mitochondrial function in subjects that are insulin sensitive, but
improves mitochondrial function in subjects that are insulin resistant. The investigators
will use a dual-site, 12- week drug intervention trial performed in a double-blind,
placebo-controlled manner on 148 subjects recruited from two separate sites (Oklahoma Medical
Research Foundation (OMRF) and University of Wisconsin-Madison (UWM)). After consent and
initial subject screening for chronic disease, subjects will be stratified to insulin
sensitive (IS) or insulin resistant (IR) groups. Over a 12- week intervention, half of each
group will take metformin and half will take a placebo. Pre- and post--intervention, subjects
will complete a series of procedures to assess insulin sensitivity, glucose regulation, and
biomarkers of aging. The same subjects will provide a skeletal muscle biopsy pre-- and
post-intervention to assess the change in mitochondrial function and mitochondrial remodeling
with and without metformin treatment. By completion of this project, the investigators expect
to provide evidence that helps further delineate who may benefit from metformin treatment to
slow aging.
Adam Konopka
All
40 Years to 75 Years old
Phase 3
This study is also accepting healthy volunteers
NCT04264897
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• 40-75 years of age (inclusive)
• Free of chronic disease
• Comprehension of the protocol as indicated by an ability to respond to questions about
the study after reading the consent form.
• Able to use and be contacted by telephone.
• Able to speak, read, and understand English, and complete a questionnaire in English
• Independently mobile
Exclusion Criteria:
• Pregnancy
• Heart disease (history, abnormal ECG, abnormal stress ECG)
• Cerebrovascular disease (history)
• Cancer (history)
• Chronic respiratory disease (history, forced expiratory volume at one second/forced
vital capacity [FEV1/FVC] < 70, FEV1 < 80% predicted)
• Chronic liver disease (history, alanine transaminase [ALT] > 52 IU/L)
• Diabetes (history, HbA1C ≥ 6.5, fasting blood glucose≥126 mg/dl, oral glucose
tolerance test [OGTT] ≥ 200 mg/dl at 2 hrs)
• Impaired kidney function (eGFR ,45 mL/min)
• B12 lab values outside of normal range (<193 or >982 pg/mL)
• Alzheimer's (history)
• Chronic kidney disease (history, abnormal blood kidney panel including serum
creatinine > 1.4)
• Problems with bleeding, on medication that prolongs bleeding time (if subject cannot
safely stop prior to biopsy)
• Those on glucose lowering drugs
• Those planning to have imaging that requires intravenous contrast dye (within 6 weeks)
or are on any of the following medications since they are contraindicated with the use
of metformin: Dofetilide, Lamotrigine, Pegvisomant, Somatropin, Trimethoprim,
Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine
• Tobacco use
• Allergies to lidocaine or metformin
AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid
The primary purpose of this study is to determine whether treatment with lecanemab is
superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite
5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with
lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by
amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial). This study
will also evaluate the long-term safety and tolerability of lecanemab in participants
enrolled in the Extension Phase.
Cynthia Carlsson, MD
All
55 Years to 80 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04468659
Show full eligibility criteria
Hide eligibility criteria
Inclusion criteria:
Participants must meet all of the following criteria to be included in this study:
1. Male or female, age 55 to 80 years inclusive at the time of informed consent, with a
plasma biomarker result that is predictive of intermediate or elevated brain amyloid
at Screening or known before Screening to have elevated or intermediate amyloid
according to previous PET, cerebrospinal fluid (CSF), or plasma testing
• Those 55 to 64 must have 1 of the following additional risk factors, given the
relatively low rates of amyloid positivity less than (<) 65 years, before screening:
• First degree relative diagnosed with dementia onset before age 75, or
• Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or
• Known before screening to have elevated brain amyloid according to previous
plasma biomarker results, PET imaging, or CSF testing
2. Global Clinical Dementia Rating (CDR) score of 0 at screening
3. Mini Mental State Examination score greater than or equal to (>=) 27 (with educational
adjustments) at screening.
4. Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at
screening of >=6
5. A45 Trial: Elevated brain amyloid pathology by amyloid PET: defined as approximately
greater than (>) 40 Centiloids on screening scan A3 Trial: Intermediate levels of
brain amyloid pathology by amyloid PET: defined as approximately 20 to 40 Centiloids
on screening scan
6. Has a study partner that is willing to participate as a source of information and has
approximately weekly contact with the participant (contact can be in-person, via
telephone or electronic communication). The study partner must have sufficient contact
such that the investigator feels the study partner can provide meaningful information
about the participant's daily function
7. Provide written (or electronic, if allowed per country-specific regulations) informed
consent
8. Willing and able to comply with all aspects of the protocol
For extension phase :
1. Completed the Core Study, or meet the following progression criteria during the Core
Study:
• Two consecutive CDR visits with Global Scores > zero when measured at least 6
months apart within the Core Study
• The principal investigator's confirmation that the participant has clinically
declined consistent progression to EAD
2. Must continue to have a study partner who is willing and able to provide follow-up
information on the participant throughout the course of the Extension Phase. The study
partner must provide separate written informed consent for the Extension Phase. Study
partners must continue to have sufficient contact such that the investigator feels the
study partner can provide meaningful information about the participant's daily
functions
3. Provide written informed consent for the Extension Phase. If a participant lacks
capacity to consent in the investigator's opinion, the participant's assent should be
obtained, if required and in accordance with local laws, regulations, and customs,
plus the written informed consent of a legal representative (capacity to consent and
the definition of a legal representative should be determined in accordance with
applicable local laws and regulations). In countries where local laws, regulations,
and customs do not permit participants who lack capacity to consent to participate in
this study (example, Spain), they will not be enrolled
4. Willing and able to comply with all aspects of the protocol
Exclusion criteria:
Participants who meet any of the following criteria will be excluded from this study:
1. Females who are breastfeeding or pregnant at screening or baseline
2. Females of childbearing potential who:
• Within 28 days before study entry, did not use a highly effective method of
contraception For sites outside of Europe, it is permissible that if a highly
effective method of contraception is not appropriate or acceptable to the participant,
then the participant must agree to use a medically acceptable method of contraception
3. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of
screening
4. Current or history within the past 2 years of psychiatric diagnosis or symptoms that,
in the opinion of the investigator, could interfere with study procedures
5. Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including
cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and
cardiac devices other than those approved as safe for use in MRI scanners), or exhibit
other significant pathological findings on brain MRI at Screening
6. Hypersensitivity to any monoclonal antibody treatment
7. Any immunological disease which is not adequately controlled, or which requires
treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of
monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the
study
8. Bleeding disorder that is not under adequate control (including a platelet count
<50,000 or international normalized ratio [INR] >1.5) at screening
9. Results of laboratory tests conducted during screening that are outside the following
limits:
• Thyroid stimulating hormone (TSH) above normal range
• Abnormally low (below lower limit of normal [LLN]) serum vitamin B12 levels for
the testing laboratory (if participant is taking vitamin B12 injections, level
should be at or above the LLN for the testing laboratory). A low vitamin B12 is
exclusionary, unless the required follow-up labs (homocysteine and methylmalonic
acid [MMA]) indicate that it is not physiologically significant
10. Known to be human immunodeficiency virus (HIV) positive
11. Any other clinically significant abnormalities that in the opinion of the investigator
require further investigation or treatment or may interfere with study procedures or
safety
12. Malignant neoplasms within 3 years of screening (except for basal or squamous cell
carcinoma in situ of the skin, or localized prostate cancer in male participants with
treatment cycles completed at least 6 months before screening). Participants who had
malignant neoplasms but who have had at least 3 years of documented uninterrupted
remission before screening need not be excluded
13. Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type
4 or 5, or any suicidal behavior assessment within 6 months before screening, at
screening, or at baseline, or has been hospitalized or treated for suicidal behavior
in the past 5 years before screening
14. Known or suspected history of drug or alcohol abuse or dependence within 2 years
before screening or a positive urine drug test at screening. Participants who test
positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug
testing need not be excluded unless in the clinical opinion of the investigator this
is due to potential drug abuse
15. Taking prohibited medications
16. Participation in a clinical study involving:
• Any anti-amyloid plaque lowering immunotherapy (example, therapeutic monoclonal
antibody or active anti-amyloid vaccine) at any time, unless it can be documented
that the participant was randomized to placebo or never received study drug
• Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless
it can be documented that the participant was randomized to placebo or never
received study drug
• Lecanemab
• Any new chemical entities or investigational drug for AD within 6 months before
randomization unless it can be documented that the participant received only
placebo
• Any other investigational medication or device study in the 8 weeks or 5
half-lives (whichever is longer) of the medication before randomization unless it
can be documented that the participant was in a placebo treatment arm
17. Planned surgery during the pre-randomization phase or within 3 months of
randomization, which requires general anesthesia
For extension phase:
1. Discontinued from the Core Study or from study treatment
2. Under study drug interruption due to ARIA or other AE at the time of transition to the
extension phase
Prospective Multi-Center Randomized Study for Evaluating the EVAHEART®2 Left Ventricular Assist System (COMPETENCE)
This is a prospective, multi-center, unblinded, randomized, controlled, and non-inferiority
study comparing the EVA2 LVAS to the most recent magnetically levitated centrifugal LVAS (HM3
LVAS).
Yu Xia
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT01187368
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
The following is a list of general inclusion criteria:
• Age ≥ 18 years
• Left Ventricular Ejection Fraction (LVEF) < 30%
• NYHA Class III with dyspnea upon mild physical activity or Class IV heart failure
• Inotrope dependent OR Cardiac Index (CI) < 2.2 L/min/m2, while not on inotropes
• Patient is able to provide written informed consent
• More detailed inclusion criteria information is noted in the study protocol
Exclusion Criteria:
1. Etiology of heart failure due to or associated with uncorrected thyroid disease,
obstructive cardiomyopathy, pericardial disease, amyloidosis, or restrictive
cardiomyopathy
2. Technical obstacles which pose an inordinately high surgical risk
3. Existence of ongoing mechanical circulatory support (MCS) other than IABP and Impella
5.0 or 5.5
4. Ongoing Impella (5.0 or 5.5) presenting related clinical sign (i.e. hematuria) and
elevated LDH equal or greater than 600 IU/L.
5. Positive pregnancy test if of childbearing potential
6. Presence of mechanical aortic cardiac valve that will not be either converted to a
bioprosthesis
7. History of any organ transplant
8. Platelet count <100,000/mL
9. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychosocial
issues
10. History of confirmed, untreated abdominal aortic aneurysm (AAA) > 5 cm in diameter
within 6 months of enrollment
11. Presence of an active, uncontrolled infection
12. Intolerance to anticoagulant or antiplatelet therapies or any other peri/postoperative
therapy that the investigator will require based upon the patient's health status
13. Presence of remarkable pre-defined end-organ dysfunction.
14. Patient has moderate to severe aortic insufficiency without plans for correction
during pump implant
15. Low albumin •removed from recent exclusion criteria
16. Planned Bi-VAD support prior to enrollment
17. Patient has known hypo- or hyper coagulable state such as disseminated intravascular
coagulation and heparin induced thrombocytopenia (HIT)
18. Participation in any other clinical investigation that is likely to confound study
results or affect the study
19. Any condition other than heart failure that could limit survival to less than 24
months
20. Patients refusing blood transfusion
Making Informed Choices on Incorporating Chemoprevention Into Care (MiCHOICE)
This trial studies the implementation of web-based decision support tools for patients with
atypical hyperplasia or lobular carcinoma in situ and healthcare providers. Decision support
tools are designed to improve informed choice about breast cancer chemoprevention.
Recognizing barriers and facilitators that can influence the adoption of decision support
tools at recruitment centers may help researchers learn how to best implement them into
clinical practice.
Kari Wisinski, MD
All
Not specified
N/A
This study is also accepting healthy volunteers
NCT04496739
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients must have histologically-confirmed atypical hyperplasia (AH) or lobular
carcinoma in situ (LCIS) documented by breast pathology report at any time in the
past. Patients with borderline breast lesions and pleomorphic LCIS are also eligible
• Patients must be women at least 35 and no more than 74 years of age at registration,
since the Breast Cancer Surveillance Consortium (BCSC) risk calculator is valid only
for this age range
• Both pre/perimenopausal and postmenopausal women are eligible
• Patients must be able to read and write in English or Spanish since study
questionnaires and educational materials are only available in English and Spanish
• Baseline questionnaires must be completed prior to patient registration
• The S1904 Patient Contact form must be completed prior to patient registration
• Patients must be able to access the internet and receive email or text messages. This
is required to access study materials and receive email/text message reminders from
the S1904 Study Team at Columbia University Irving Medical Center (CUIMC). The patient
decision aid, RealRisks, is accessible via smartphones, tablets, or personal
computers. If patients do not own these devices, local study personnel will provide
resources for patients to access RealRisks via computer kiosks or tablets in clinic
waiting rooms or public locations, such as community centers or public libraries
• Patients and healthcare providers must be informed of the investigational nature of
this study and must sign and give written informed consent in accordance with
institutional and federal guidelines
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
• IMPLEMENTATION: Providers who enrolled in S1904 at Group 2 (intervention) recruitment
center and consented to future contact are eligible to participate in the interviews
• IMPLEMENTATION EVALUATION: Patients who registered to S1904 at a Group 2
(Intervention) Recruitment Center and consented to be contacted for future research
are eligible to participate in the interviews
• Recruitment Centers must be National Clinical Trials Network (NCTN), National Cancer
Institute Community Oncology Research Program (NCORP) or Minority Underserved
(MU)-NCORP institutions
• Recruitment Centers must have an active EHR and patient portal used in the outpatient
clinics which is common and accessible across all sites belonging to the Recruitment
Center
• Recruitment Centers must be willing to allow the S1904 study team access to the site's
application program interface (API) for integration of the study materials (standard
educational materials and decision support tools) into the EHR and patient portal.
(NOTE: Both Group 1 (control) and Group 2 (intervention) recruitment centers may
access the standard educational materials via the patient portal or uniform resource
locator (URL)/website)
• Recruitment centers must see at least 50 AH and/or LCIS patients per year
• Recruitment centers must identify a lead principal investigator (PI) to facilitate
recruitment and retention of patients and healthcare providers and to participate in
quarterly stakeholder meetings/conference calls
• Recruitment centers must be willing to register at about 16 patients and 5 healthcare
providers to the study
• Recruitment Centers must be willing to submit monthly screening logs to CUIMC
• Providers must regularly see patients with AH or LCIS at an approved recruitment
center
• Providers must be willing to provide informed consent and complete an online baseline
questionnaire
• Providers who will register patients must be registered members of a Cooperative Group
• Providers who register patients to S1904 must be willing to see those same patients
for their 6-month study visits, as the provider intervention tools require that the
"treating investigator" as designated in OPEN and the provider at the 6-month study
visit be the same
Exclusion Criteria:
• Patients must not have a history of invasive breast cancer or ductal carcinoma in situ
• Patients must not have prior or current use of selective estrogen receptor modulators
(SERMs) or aromatase inhibitors (AIs)
• NOTE: The following are approved SERMS and AIs, however, the study is not limited
to these.
• SERMs: tamoxifen, raloxifene
• AIs: anastrozole, exemestane, letrozole
• Patients must not be currently taking hormone replacement therapy
• Patients must not have a history of bilateral mastectomies or breast implants since
the risk calculator is not applicable to these women
• Patients must not be pregnant or lactating
• Premenopausal patients must not have a history of thromboembolism, since it is a
contraindication to tamoxifen. Tamoxifen is the only Food and Drug Administration
(FDA)-approved drug for breast cancer chemoprevention among high-risk premenopausal
women, whereas postmenopausal women are eligible for both SERMs and AIs
Atypical Hyperplasia of the Breast, Lobular Breast Carcinoma In Situ, Pleomorphic Lobular Breast Carcinoma In Situ, Breast
Immunonutrition Supplementation for Improved Burn Wound Healing in Older Adults
This pilot study aims to assess the feasibility of providing immunonutrition supplementation
to older burn patients (age 55 and older) and its impact on burn wound healing. Supplements
containing arginine and omega 3 fatty acids have been shown to have beneficial effects on
healing in other types of wounds but data within the burn population remains limited. 20
participants will be randomized into two arms, immunonutrition or conventional supplement and
can expect to be on study for 3 months.
Rebecca Busch
All
55 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04725071
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Subject has partial of full thickness thermal injury of 1-15% of total body surface
area (TBSA)
• Subject has an inpatient admission for their burn
• Subject or authorized decision maker understands the study procedures and can provide
informed consent to participate in the study and authorization for release of relevant
protected health information to the study investigator
Exclusion Criteria:
• Subject with inhalation injury and/or intubation
• Subject receiving immunosuppressive medications including chronic steroids, immune
modulating medications, and chemotherapy prior to admission
• Subject with pre-existing severe chronic liver disease or end stage renal disease
Burn Wound, Burn of unspecified body region, unspecified degree, Burns and corrosions of external body surface, Burns involving 10-19% of body surface area, Burns involving less than 10% of body surface, Other, Injury, Trauma & Emergency Medicine, Food & Nutrition, Skin & Dermatology
Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
This phase III trial compares the combination of four drugs (daratumumab, bortezomib,
lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab,
lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, 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. Daratumumab is a monoclonal antibody
that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory
drugs, such as dexamethasone lower the body's immune response and are used with other drugs
in the treatment of some types of cancer. Adding bortezomib to daratumumab, lenalidomide, and
dexamethasone may be more effective in shrinking the cancer or preventing it from returning,
compared to continuing on daratumumab, lenalidomide, and dexamethasone.
Timothy Schmidt, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04566328
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• STEP 0 •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance
status (PS) of 0-2 (PS 3 allowed if secondary to pain)
• STEP 0 •Patient must have newly diagnosed multiple myeloma (MM) by International
Myeloma Working Group (IMWG) criteria
• STEP 0 •Patient must agree to register to the mandatory REVLIMID Risk Evaluation and
Mitigation Strategy (RevREMS) program and be willing and able to comply with the
requirements of RevREMS
• STEP 0 •Patient must be able to undergo diagnostic bone marrow aspirate following
preregistration.
• NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies
for clonoSEQ Assay
• NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from
the Clonality (ID) test within fourteen (14) days of receipt and reconciliation
of fresh bone marrow specimen to the submitting institution
• STEP 1 •Patient must meet all eligibility criteria in STEP 0 with exception of
allergy requirement
• STEP 1 •Institution must have received the Clonality (ID) test results from Adaptive
Biotechnologies and dominant sequences were identified
• STEP 1 •Patient must have standard risk MM as defined by the Revised International
Staging System (RISS) stage I or II
• NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate
dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA)
detected by interphase fluorescent in situ hybridization (iFISH). Presence of
del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these,
including any other findings, are standard risk
• R-ISS stage
• Stage I: ISS stage I [beta2 macroglobulin < 3.5 mg/L, albumin > 3.5 g/dL]
AND standard-risk CA AND normal LDH
• Stage II: Not R-ISS stage I or III
• Stage III: ISS stage III [beta2 macroglobulin > 5.5 mg/L] AND high-risk CA
OR high LDH (> upper limit of normal) [patients with stage III are
ineligible]
• STEP 1 •Patient must have measurable or evaluable disease as defined by having one or
more of the following, obtained within 28 days prior to registration:
• >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
• >= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein
electrophoresis
• Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
• Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
• STEP 1 •Patients must have a serum protein electrophoresis (SPEP), urine protein
electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28
days prior to registration. In addition, a bone marrow biopsy and/or aspirate is
required within 28 days if bone marrow is being followed for response
• NOTE: UPEP (on a 24-hour collection) is required, no substitute method is
acceptable. Urine must be followed monthly if the baseline urine M-spike is >=
200 mg/24 hr. Please note that if both serum and urine M-components are present,
both must be followed in order to evaluate response
• NOTE: The serum free light chain test is required to be done if the patient does
not have measurable disease in the serum or urine. Measurable disease in the
serum is defined as having a serum M-spike >= 1 g/dL. Measurable disease in the
urine is defined as having a urine M-spike >= 200 mg/24 hr
• STEP 1 •Calculated creatinine clearance > 30 mL/min (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
Step 1 registration)
• STEP 1 •Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to Step
1 registration)
• STEP 1 •Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained
=< 14 days prior to Step 1 registration)
• STEP 1 •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
ULN (obtained =< 14 days prior to Step 1 registration)
• STEP 1 •Patient must have received no more than one cycle (28 days or less) of prior
chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed
to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to
symptomatic lesions is allowed provided there are no residual toxicity related to
radiation and blood counts meet the study requirements. Radiation treatment must be
completed at least 14 days prior to Step 1 registration
• STEP 1 •Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months of randomization
are eligible for this trial
• STEP 1 •For patients with evidence of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy, if indicated
• STEP 1 •Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
• STEP 1 •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
• STEP 1 •Patients with known history or current symptoms of cardiac disease, or
history of treatment with cardiotoxic agents, should have a clinical risk assessment
of cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, patients should be class 2B or better. Patients must not
have evidence of current uncontrolled cardiovascular conditions, including
hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or
myocardial infarction within 6 months prior to Step 1 registration
• STEP 1 •Patient may have a history of current or previous deep vein thrombosis (DVT)
or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation
as prophylaxis if they are not currently on full-dose anticoagulation
• STEP 1 •Patients with a history of chronic obstructive pulmonary disease (COPD) must
have FEV1 testing done within 28 days prior to Step 1 registration and the forced
expiratory volume in 1 second (FEV1) must be > 50% of predicted normal
• STEP 2 •Institution must have received Tracking (MRD) test results from Adaptive
Biotechnologies
• STEP 2 •Patient must have completed the Step 1 Induction phase of this protocol
without experiencing progression
• STEP 2 •Patient must be registered to Step 2 within 8 weeks of completing Step 1
Induction Treatment, counting from last day of completion of last cycle
• STEP 2 •Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if
secondary to pain)
• STEP 2 •Any adverse event(s) related to Step 1 Induction Treatment must have resolved
to grade 2 or less
• STEP 2 •Hemoglobin >= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
• STEP 2 •Platelet count >= 50,000/mm^3 (obtained within 14 days prior to Step 2
randomization)
• STEP 2 •Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Calculated creatinine clearance >= 30 mL/min (obtained within 14 days prior
to Step 2 randomization)
• STEP 2 •Total bilirubin =< 1.5 x ULN (Institutional upper limit of normal) (obtained
within 14 days prior to Step 2 randomization)
• STEP 2 •ALT and AST < 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
• STEP 0 •Patient must not have any known allergies, hypersensitivity, or intolerance
to corticosteroids, monoclonal antibodies or human proteins, or their excipients
(refer to respective package inserts or Investigator's Brochure), or known sensitivity
to mammalian-derived products
• STEP 1 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 1 registration to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• 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)
• STEP 1 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception). Men must not expect to father children by practicing true abstinence
from sexual intercourse for the duration of their participation in the study (periodic
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and
withdrawal are not acceptable methods of contraception) OR use a latex condom during
sexual contact with a female of child bearing potential while participating in the
study and for at least 3 months after the last dose of protocol treatment even if they
have had a successful vasectomy. Men must also agree to abstain from donating sperm
while on study treatment and for 3 months after the last dose of protocol treatment
even if they have had a successful vasectomy. Both women and men must both agree to
abstain from donating blood during study participation and for at least 28 days after
the last dose of protocol treatment
• STEP 1 •Patient must not have peripheral neuropathy >= grade 2 on clinical
examination or grade 1 with pain at time of Step 1 registration
• STEP 1 •Patient must not have any serious medical or psychiatric illness that could,
in the investigator's opinion, potentially interfere with the completion of treatment
according to this protocol
• STEP 1 •Patient must not have moderate or severe persistent asthma within the past 2
years, or uncontrolled asthma of any classification
• NOTE: Patients who currently have controlled intermittent asthma or controlled
mild persistent asthma are allowed to register
• STEP 1 •Patient must not receive any other concurrent chemotherapy, or any ancillary
therapy considered investigational while on this protocol
• NOTE: Bisphosphonates are considered to be supportive care rather than therapy,
and are thus allowed while on protocol treatment
• STEP 2 •Patient must not have received any non-protocol therapy outside of the
assigned Step 1 Induction treatment including stem cell transplant
• STEP 2 •Women must not be pregnant or breast-feeding due to the potential harm and
teratogenic effects to an unborn fetus and possible risk for adverse events in nursing
infants with the treatment regimens being used. All females of childbearing potential
must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within
10-14 days prior to Step 2 randomization to rule out pregnancy and again within 24
hours prior to the first dose of lenalidomide. Females of childbearing potential must
also agree to ongoing pregnancy testing while on protocol treatment. A female of
childbearing potential is defined as any woman, regardless of sexual orientation or
whether they have undergone tubal ligation, who meets the following criteria:
• Has achieved menarche at some point,
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• 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).
• STEP 2 •Women of childbearing potential must not expect to conceive children by using
accepted and effective method(s) of contraception (for this protocol defined as the
use of TWO acceptable methods of birth control, one highly effective method and one
additional effective method AT THE SAME TIME for 1) at least 28 days before starting
protocol treatment; 2) while participating in the study; 3) during dose interruptions;
and 4) for at least 3 months days after the last dose of protocol treatment) OR by
practicing true abstinence from sexual intercourse for the duration of their
participation in the study (periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of
contraception).
Men must not expect to father children by practicing true abstinence from sexual
intercourse for the duration of their participation in the study (periodic abstinence
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not
acceptable methods of contraception) OR use a latex condom during sexual contact with a
female of child bearing potential while participating in the study and for at least 3
months after the last dose of protocol treatment even if they have had a successful
vasectomy. Men must also agree to abstain from donating sperm while on study treatment and
for 3 months after the last dose of protocol treatment even if they have had a successful
vasectomy. Both women and men must both agree to abstain from donating blood during study
participation and for at least 28 days after the last dose of protocol treatment
Plasma Cell Myeloma, RISS Stage I Plasma Cell Myeloma, RISS Stage II Plasma Cell Myeloma, Multiple Myeloma
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with
newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology
Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such
as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan)
and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) 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. This trial may help doctors find out
what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and
standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen
ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with
3 or more drugs for the initial WT).
Kenneth Desantes, M.D.
All
up to 30 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04322318
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Patients with newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if
anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a
delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed
nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an
eligibility requirement for patients with relapsed favorable histology Wilms tumor.
• Patients must be =< 30 years old at study enrollment
• Patients with the following diagnoses are eligible for this study:
• Newly diagnosed stages 2 •4 diffuse anaplastic Wilms tumor as confirmed by
central review
• Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must
have previously achieved remission for their initial FHWT diagnosis to be
eligible for this study. The relapse risk groups are defined as follows,
regardless of radiation therapy:
• Standard-Risk relapse: Patients who received two chemotherapy agents for
frontline therapy; primarily actinomycin D and vincristine
• High-Risk relapse: Patients who received three chemotherapy agents for
frontline therapy; primarily vincristine, actinomycin D and doxorubicin or
vincristine, actinomycin D and irinotecan
• Very High-Risk relapse: Patients who received four or more chemotherapy
agents as part of initial therapy; primarily regimen M or its variations
• Patients with newly diagnosed DAWT must have had histologic verification of the
malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but
not required
• Note: For relapsed FHWT patients, an institutional pathology report confirming
favorable histology Wilms tumor (from relapse, if available, or from original
diagnosis) must be available for upload prior to initiation of protocol therapy
• Patients with newly diagnosed Stages 2 •4 diffuse anaplastic Wilms tumor must be
enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure
that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or
delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior
therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse
anaplastic Wilms tumor at subsequent review of the initial biopsy
• Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least
1 lymph node sampled prior to study enrollment
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have
had no prior systemic therapy, except in the following situations:
• Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks
of pre nephrectomy chemotherapy for what was originally presumed to be favorable
histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms
tumor at delayed nephrectomy
• Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of
chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for
presumed favorable histology Wilms tumor based on institutional review, but
subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2
initial risk assignment results (if available per current version of AREN03B2)
• Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an
emergent basis and within allowed timing as described
• Note: Patients who received prior therapy for presumed favorable histology Wilms
tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must
begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who
received emergency radiation to preserve organ function are eligible as noted.
Patients who received radiation as part of standard of care for presumed newly
diagnosed favorable histology Wilms tumor, along with chemotherapy as noted
above, prior to identification of diffuse anaplasia, are also eligible
• Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior
chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In
addition, patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study
• Radiation therapy (RT): >= 2 weeks (wks) must have elapsed for local palliative
RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >=
50% radiation of pelvis; >= 6 wks must have elapsed if other substantial bone
marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who
received emergency radiation to preserve organ function are eligible and do not
need to washout with the above criteria
• Patients may not be receiving any other investigational agents (within 4 weeks prior
to study enrollment)
• Peripheral absolute neutrophil count (ANC) >= 750/uL (performed within 7 days prior to
enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior
to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed
within 7 days prior to enrollment)
• Patients with high-risk or very high-risk relapsed FHWT who will be treated with
regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or
radioisotope glomerular filtration rate (GFR) and meet the following requirement:
• Creatinine clearance or radioisotope GFR >= 60 mL/min/1.73 m^2 (performed within
7 days prior to enrollment)
• Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be
treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR
(meeting the above criteria of GFR >= 60 mL/min/1.73 m^2), or an adequate serum
creatinine as per the following table:
• Age: Maximum Serum Creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male and female)
• 6 months to < 1 year: 0.5 (male and female)
• 1 to < 2 years: 0.6 (male and female)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male), 1.4 (female)
• >= 16 years: 1.7 (male), 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =<
ULN for patients whose total bilirubin > 1.5 x ULN (performed within 7 days prior to
enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age or =< 5 x ULN for patients with liver metastases
(performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram (obtained within 21 days prior to enrollment and start of
protocol therapy)
Exclusion Criteria:
• Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
• Patients with any uncontrolled, intercurrent illness including, but not limited to,
ongoing or active infection, or symptomatic congestive heart failure (defined as grade
2 or higher heart failure per Common Terminology Criteria for Adverse Events [CTCAE]
version 5.0)
• Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk
FHWT initially observed without chemotherapy) or received only one chemotherapy agent
for frontline therapy
• For patients with high-risk or very high-risk relapsed FHWT:
• Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate < 16
mmol/L and serum phosphate =< 2 mg/dL (or < 0.8 mmol/L) without supplementation
• For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
• Chronic inflammatory bowel disease and/or bowel obstruction
• Concomitant use of St. John's wort, which cannot be stopped prior to the start of
trial treatment
• 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
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Kidney
Inotuzumab Ozogamicin and Blinatumomab in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating
patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed,
has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies,
such as inotuzumab ozogamicin and blinatumomab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread.
Ryan Mattison, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03739814
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pre-registration Eligibility Criteria (Step 0)
• Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory
prior to registration; the bone marrow sample should be from the first aspiration
(i.e. first pull). Aspirate needle should be redirected if needed to get first pull
bone marrow aspirate. It should be initiated as soon as possible after
pre-registration. The specimens should be sent to the HEME Biobank.
• Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:
• Patients may receive the day 1 of course IA dose of intrathecal (IT)
methotrexate during the prior-to-registration lumbar puncture (or the venous
line placement) to avoid a second lumbar puncture. If the dose is
administered prior to registration, then systemic chemotherapy must begin
within 7 days of this IT chemotherapy.
• Registration Eligibility Criteria (Step 1)
• Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on
World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are
not eligible.
• CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local
hematopathology evaluation.
• Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, fluorescence in situ
hybridization (FISH), and/or polymerase chain reaction (PCR). If any test is positive
for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.
• No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed).
Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the
cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease
within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve
palsies or other significant neurological dysfunction) within the 28 days prior to
registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for
additional guidance. Prophylactic intrathecal medication alone is not an exclusion.
• Categories of CNS Involvement for CNS Evaluation Prior to Registration:
• CNS 1: CSF has < 5 WBC/uL with cytospin negative for blasts; or >= 10 red
blood cell (RBC)/uL with cytospin negative for blasts.
• CNS 2: CSF has < 5 WBC/uL with cytospin positive for blasts; or >= 10 RBC/uL
with cytospin positive for blasts; or >= 10 RBC/uL, WBC/uL >= 5 but less
than Steinherz/Bleyer algorithm with cytospin positive for blasts (see
below).
• CNS 3: CSF has >= 5 WBC/uL with cytospin positive for blasts; or >= 10
RBC/uL, >= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below);
or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye
involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating
Initial Traumatic Lumbar Punctures:
• If the patient has leukemia cells in the peripheral blood and the
lumbar puncture is traumatic and contains >= 5 WBC/uL with blasts, the
following algorithm should be used to define CNS disease: CSF WBC/CSF
RBC > 2 x (Blood WBC/Blood RBC count)
• Patients with known or suspected testicular involvement by leukemia are allowed
provided that the patient receives concomitant scrotal/testicular radiotherapy.
• Unilateral or bilateral testicular enlargement should be assessed by ultrasound
or other imaging technique. Biopsy is recommended if clinical findings are
equivocal or suggestive of hydrocele or a non-leukemic mass, but further
assessments are per treating physician discretion.
• Not pregnant and not nursing.
• This study involves agents that have known genotoxic, mutagenic, and teratogenic
effects. Therefore, for women of childbearing potential only, a negative
pregnancy test done =< 7 days prior to registration is required.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
• No unstable cardiac disease such as myocardial infarction, angina pectoris,
uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of
registration.
• No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) <
45% or New York Heart Association (NYHA) stage III or IV congestive heart failure
(CHF).
• Patients with known human immunodeficiency virus (HIV) infection are eligible if they
have been on effective antiretroviral therapy with an undetectable viral load tested
within 6 months of registration.
• Patients with hepatitis B virus (HBV) are eligible only if they meet all the
following:
• On HBV-suppressive therapy.
• No evidence of active virus.
• No evidence of HBV-related liver damage.
• Patients with hepatitis C virus (HCV) are eligible only if they meet all the
following:
• Successfully completed complete-eradication therapy with undetectable viral load.
• No evidence of HCV-related liver damage.
• No history of clinically relevant neurologic disorder such as epilepsy, seizure,
aphasia, stroke, severe brain injury, structural brain abnormality, benign brain
tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other
significant CNS abnormalities.
• No prior additional malignancy (i.e. in addition to ALL) except adequately treated
basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer
from which the patient is currently in complete remission, or any other cancer from
which the patient has been disease-free for >= 2 years.
• No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal
syncope, or chronic bradycardic states such as sinoatrial block or higher degree of
atrioventricular block unless a permanent pacemaker has been implanted.
• No history of chronic liver disease, including cirrhosis.
• No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
• No uncontrolled infection or recent history (within 4 months prior to registration) of
deep tissue infections such as fasciitis or osteomyelitis.
• Total bilirubin, serum =< 1.5 x upper limit of normal (ULN)*
• Except in the event of: 1) Gilbert disease, in which case total bilirubin must be
=< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to
leukemic infiltration, in which case total bilirubin must be =< 2 x ULN.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine, serum =< 1.5 ULN OR creatinine clearance >= 40 mL/min
• QT interval by Fridericia's correction formula (QTcF) =< 470 msec
• Cohort 1 Patients Only
• Age >= 60 years.
• No prior treatment for ALL except a single dose of intrathecal chemotherapy,
corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count
and prevent ALL complications. Allowed therapy may be administered for no more than 14
days and must be completed >= 24 hours prior to the initiation of protocol therapy.
• No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
• Cohort 2 Patients Only:
• Age >= 18 years.
• Relapsed or refractory disease in salvage 1 or 2.
• No isolated extramedullary relapse.
• Prior allogeneic HCT permitted.
• Patients with prior allogeneic HCT must have completed transplantation >= 4 months
prior to registration.
• Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease
and must have completed immunosuppressive therapy >= 30 days prior to registration.
• Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy,
or other CD19-directed therapy is not allowed.
• Prior treatment with rituximab must be completed >= 7 days prior to registration.
• Prior treatment with other monoclonal antibodies must be completed >= 6 weeks prior to
registration.
• Prior treatment for ALL must be completed >= 14 days prior to registration with the
following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids,
6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce
circulating absolute lymphoblast count to =< 10,000/uL or prevent complications
related to ALL are allowed but must be completed >= 24 hours prior to the initiation
of protocol therapy.
• Patients should have resolution of any acute non-hematologic toxicities of prior
therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE) version (v)5.0 grade =< 1.
• Peripheral blood absolute lymphoblast count =< 10,000/uL (treatment allowed as above
to reduce blast count to =< 10,000/uL)
B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Leukemia
Parenteral Ascorbic Acid Repletion in TransplantatIon (PARTI)
A single-center, randomized, double-blinded placebo-controlled trial is proposed to
investigate administration of supraphysiologic doses of ascorbic acid (vitamin C, AA) to
patients undergoing liver transplantation. Participants randomized to the intervention group
will receive intravenous (IV) AA 1500 mg every 6 hours for 48 hours. Participants randomized
to the control group will receive a saline placebo. The primary study outcome will be a
change in the Sequential Organ Failure Assessment (SOFA) score from baseline to three days
after the first dose of drug (dSOFA3). Secondary outcomes will include total vasopressor dose
in norepinephrine equivalents, 30-day and 1-year mortality, and serum AA levels.
Molly Groose
All
18 Years to 80 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT04756063
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• The subject is scheduled to undergo primary deceased donor solidary liver
transplantation
Exclusion Criteria:
• Non-English speaking
• Known or believed to be pregnant
• Subject is a prisoner
• Impaired decision-making capacity (i.e., current encephalopathy)
• Known allergy to AA
• Concurrent organ transplantation (i.e., simultaneous liver-kidney transplantation)
• Planned veno-venous bypass use in the operating room
• Prior parenteral or oral AA repletion
• History of nephrolithiasis or oxaluria
• Vitamin C supplement use or administration (including HAT therapy) within the last
month prior to transplantation
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Sickle cell anemia
• Hereditary hemochromatosis
• Preoperative anuria or creatinine >2.5mg/dL in patient not on renal replacement
therapy
• Current enrollment in another research study
Liver Transplant Failure and Rejection, Other, Transplant, Digestive Health & Liver Disease
The goal of this study is to establish a birth cohort that collects prenatal and early life
biosamples and environmental samples and rigorously phenotypes young children for food
allergy and Atopic Dermatitis (AD) to identify prenatal and early life markers of high risk
for food allergy and AD, as well as biological pathways (endotypes) that result in these
conditions.
Primary Objectives:
- To study the role and interrelationships of established and novel clinical,
environmental, biological, and genetic prenatal and early-life factors in the
development of allergic diseases through age 3 years, with an emphasis on atopic
dermatitis and food allergy
- To apply systems biology to identify mechanisms and biomarkers underlying the
development of food allergy, atopic dermatitis, and their endotypes
- To collect, process, and assay or store environmental and biological samples for current
and future use in the study of allergic disease development
James Gern
All
0 Years and over
NA
This study is also accepting healthy volunteers
NCT04798079
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
Pregnant Women-
Pregnant women who meet all of the following criteria are eligible for enrollment as study
participants:
1. Age 18 years or older
2. Able to understand the oral and written instructions associated with study visits and
procedures and provide informed consent
3. Pregnant at any stage
4. Planning to give birth at a study-site designated center
5. Agrees to enroll offspring into the study at birth
6. In the case of multiple gestation, agrees to enroll only one child who will be
selected by randomized birth order
Biological Fathers-
Biological fathers who meet all of the following criteria are eligible for enrollment as
study participants:
1. Age 18 years or older
2. Able to understand the oral and written instructions associated with study visits and
procedures and provide informed consent
Exclusion Criteria:
Pregnant Women-
Pregnant women who meet any of these criteria are not eligible for enrollment:
1. Inability or unwillingness to comply with study protocol
2. Serious pregnancy complication (in the judgement of the investigator) prior to
enrollment
3. Fetus has a major chromosomal anomaly
4. Plans to move and would not be available for in-person visits at a study site
5. Plans to give up her child for adoption at birth
6. Pregnancy is the result of an egg donation
Infants-
Infants who meet any of these criteria are not eligible for enrollment:
1. Delivered earlier than 34 weeks of gestation
2. Sibling already enrolled
3. Born with a significant birth defect or medical condition, and in the judgment of the
investigators, participation is not in the infant's best interest
Biological Father-
1. Biological fathers who are unable or unwilling to comply with the study protocol as it
pertains to the biological father's participation are not eligible for enrollment
----Note Regarding Legal Guardians who are not the Biological Parents:
1. At screening for enrollment of either the mother or the child, if the biological
mother intends to give the infant up for adoption, neither the mother nor the child
are eligible for enrollment
2. If the biological mother gives up legal guardianship of the child during the child's
follow-up period, the child may remain enrolled as long as the new legal guardian:
• Agrees to meet the child's study requirements, and
• Provides written informed consent for the child's continued participation.
3. Throughout the protocol where it refers to the mother, father, or parent answering
questionnaires about the child or collecting samples from the child and the child's
primary home, the legal guardian who provides consent for the child's participation
may complete those procedures
Preparing for Prevention of Huntington's Disease (PREVENT-HD) (PREVENT-HD)
This is a prospective investigation which aims to address key challenges to the design of
clinical trials to prevent the onset of Huntington's disease (HD). The project will provide
necessary psychometric data for clinical outcome assessments (COAs) and biomarkers (BMs) in
the cerebral spinal fluid (CSF) to address questions of central importance to the success of
these measures for premanifest clinical trials. Of the 258 participants: 52 will be low risk
of motor diagnosis, 102 high risk of motor diagnosis, 52 with diagnosed HD (stages I or II),
and 52 healthy controls. Participants can expect to be in the study for up to 2 years.
Jane Paulsen
All
18 Years to 80 Years old
NA
This study is also accepting healthy volunteers
NCT04818060
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria for HD Participants:
• Estimated at low or high probability of motor diagnosis based on the multivariate risk
score (MRS)
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up)
and remote assessments as needed
• No active comorbidities (i.e. receiving stable treatment)
• All medications will be allowed although the protocol will mandate documentation of
medications and analyses will particularly assess potential impact of medications on
outcomes (i.e., sedation of abnormal movements)
• If previously measured, CAG results must be 36 or above (previous CAG is not a
requirement, but this threshold will be upheld for those participants who have their
CAG scores and/or have them in their medical record).
Inclusion Criteria for Healthy Controls (HC):
• Willing to commit to two in-person assessment visits (baseline and 2-year follow-up)
and remote assessments as needed
• In generally good health
• IQ > 70
• Able to undergo an MRI scan
Exclusion Criteria (for all Participants):
• Evidence of unstable medical or psychiatric illness (including substance abuse)
• History of severe learning disability, mental retardation, or other central nervous
system (CNS) disease or event (e.g., seizures, head trauma, additional neurological
diagnoses)
• Treatment with phenothiazine-derivative antiemetic medications such as
prochlorperazine, metoclopramide, promethazine and Inapsine greater than 3 times per
month
• History of serious alcohol or drug abuse within the past year
• Unable (determined by patient's prescribing doctor) to not take tryptophan, leucine,
niacin or niacinamide-containing dietary supplements, anti-inflammatory medications,
anti-coagulants (such as warfarin and heparin) or anti-platelets (such as aspirin) in
the past 14 days to assure safety during lumbar puncture
• Unable to fast (no food or drink, only water) overnight before the lumbar puncture
Intravesical Photodynamic Therapy ("PDT") in BCG-Unresponsive/Intolerant Non-Muscle Invasive Bladder Cancer ("NMIBC") Patients
This is a phase II, open-label, single-arm, multi-center Study conducted in Canada and the
United States. Patients with NMIBC CIS (with or without resected papillary disease (Ta, T1))
that are considered Bacillus Calmette-Guerin ("BCG")-Unresponsive or who are intolerant to
BCG therapy. BCG-Unresponsive is at least one of the following: At least five of six doses of
an initial induction course plus at least two of three doses of maintenance therapy; or, at
least five of six doses of an initial induction course plus at least two of six doses of a
second induction course. Patients experiencing disease relapse within 12 months after
finishing the second course of BCG therapy are considered BCG-Unresponsive. The Study will
consist of approximately 100 to 125 patients who will undergo two (2) PDT treatments
employing 0.70 mg/cm^2 of Ruvidar® (TLD-1433) at Day 0 and Day 180.
Kyle Richards, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03945162
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Be willing and able to provide a written Informed Consent Form ("ICF") for the Study.
2. Be > 18 years of age on day of signing ICF.
3. Have histologically confirmed NMIBC CIS via biopsy with/without resected papillary
disease (Ta, T1) (high grade) using the 2004 World Health Organization ("WHO") /
International Society of Urologic Pathology classification system. The most recent
cystoscopy / TURBT must have been performed within 12 weeks of the Study Treatment
date to confirm: histology, grade and stage.
4. Intolerant to BCG or considered BCG-Unresponsive, which is at least one of the
following:
• At least five of six doses of an initial induction course, plus at least two of
three doses of maintenance therapy, or
• At least five of six doses of an initial induction course, plus at least two of
six doses of a second induction course.
5. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
6. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 2.
7. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 60
minutes.
8. Are available for the duration of the Study including follow-up (approximately 15
months).
9. Female patients of childbearing potential must have a negative Human Chorionic
Gonadotropin ("HCG") pregnancy test taken during the screening visit and confirmed
prior to the Study Treatment.
10. Female patients of childbearing potential must be willing to use 2 methods of birth
control (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgically
sterile, or abstain from heterosexual activity for two weeks after the Study
Treatment. Patients of childbearing potential are those who have not been surgically
sterilized or have not been free from menses for >1 year.
Exclusion Criteria:
1. Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.
2. Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate or
prostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium.
(confirmed by staging to exclude extravesical disease, which may include radiological
imaging and/or biopsy) within 3 months of enrollment:
If previous work up occurred more than 3 months prior to enrollment, staging for
extravesical disease must be repeated prior to enrolment in order to determine
eligibility.
3. Active gross hematuria.
4. Have a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin that has undergone potentially curative therapy, in situ cervical cancer or
localized prostate cancer under active surveillance with Gleason 6 disease. A history
of prostate cancer that was treated with definitive intent (surgically or through
radiation therapy) is acceptable, provided that the following criteria are met: Stage
T2N0M0 or lower Prostate-Specific Antigen ("PSA") undetectable for 2 years while off
androgen deprivation therapy or no more than 2 consecutive rising PSAs.
5. Have a history or current evidence of any condition, therapy, surgery or laboratory
abnormality that, in the opinion of the PI, might confound the results of the Study,
interfere with the patient's participation in the Study, or is not in the best
interest of the patient to participate.
6. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1,
Prohibited Medications).
7. Participated in a study with an investigational agent or device within 1 month from
the first dose of current Study treatment.
8. Prior treatment with an intravesical chemotherapeutic agent within 1 month of the
first dose of current Study Drug, with the exception of a single perioperative dose of
chemotherapy immediately post-TURBT (not considered treatment).
9. Have an active infection requiring systemic therapy, including active or intractable
Urinary Tract Infection ("UTI"), not resolved prior to the procedure.
10. Has any contraindication to general or spinal anesthesia.
11. Is pregnant or breastfeeding within the projected duration of Study II, starting with
the screening visit through to two weeks following the second Ruvidar® (TLD-1433)
instillation.
Non-Muscle Invasive Bladder Cancer ("NMIBC") Unresponsive/Intolerant to BCG, Urinary Bladder, Bladder
Prospective Study of Pregnancy in Women With Cystic Fibrosis (MAYFLOWERS)
In this study, the investigators aim to evaluate changes in lung function in women with
cystic fibrosis (CF) during pregnancy and for 2 years after pregnancy based on exposure to
highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Erin Lowery
Female
16 Years and over
NA
This study is NOT accepting healthy volunteers
NCT04828382
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pregnant, intending to continue pregnancy, enrolled in the Cystic Fibrosis Foundation
Patient Registry (CFFPR)
Exclusion Criteria:
• None
Pregnancy Related, Cystic Fibrosis, Cystic fibrosis, Other
A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer
The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab)
taken alone or together with standard chemotherapy for the potential treatment of colorectal
cancer that:
- has spread to other parts of the body (metastatic);
- has a certain type of abnormal gene called "BRAF"; and
- has not received prior treatment.
Participants in this study will receive one of the following study treatments:
- Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home
every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection
into the vein) at the study clinic.
- Encorafenib plus cetuximab with chemotherapy: These participants will receive
encorafenib and cetuximab in the way described in the bullet above. Additionally, they
will receive standard chemotherapy by IV infusion and oral treatment at home.
- Chemotherapy alone: These participants will receive chemotherapy, the standard treatment
for this condition, by IV infusion at the study clinics and oral treatment at home.
This study is currently enrolling participants who will receive either encorafenib plus
cetuximab with chemotherapy or chemotherapy alone.
The study team will monitor how each participant responds to the study treatment for up to
about 3 years.
Dustin Deming, MD
All
16 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04607421
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Safety Lead-In = Male/female ≥ 18 years old
• Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally)
• Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E
mutation
• Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none
for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered
metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant
treatment )
• Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety
Lead-in)
• ECOG PS 0-1
• Adequate organ function
Exclusion Criteria:
• Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is
ineligible to receive immune checkpoint inhibitors due to a pre-existing medical
condition
• Active bacterial or viral infections in 2 weeks prior to starting dosing
• Symptomatic brain metastases
Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI)
biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including
fractional flow change in the portal vein and elevated azygos flow.
End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and
portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol
abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its
aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage
liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic
collaterals that shunt blood away from the liver develop due to increased portal pressure.
Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal
internal bleeding. GEV bleeding carries ~20% mortality at 6 weeks, and ~34% overall
mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance
to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines
recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of
high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%.
However, endoscopy is invasive and often unnecessary when no treatment is required.
Therefore, the American Association for the Study of Liver Diseases has identified the
development of "non-invasive markers that predict the presence of high-risk varices" as a
major unmet need.
Scott Reeder, MD, PhD
All
18 Years and over
Pilot
This study is also accepting healthy volunteers
NCT04867954
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria for Aim 1:
•
Healthy volunteers
: Adults (>18 years) with no known liver pathology
• Obese volunteers: Adults (>18 years), no known liver pathology, body mass index (BMI)
≥ 35
• Patients: Adults (>18 years) with known cirrhosis and known Gastroesophageal varices
Exclusion Criteria for Aim 1:
• contraindications to MRI
• hypersensitivity reactions to both contrast agents
• patients with recent treatment for varices with embolization, TIPS, or other
endovascular treatment
• patients with active GEV bleeding; known occlusive thrombus in portal vein, splenic
vein, or superior mesenteric vein.
• patients with large HCC with known PC involvement.
Inclusion criteria for Aim 2-4:
• Adults (>18 years) with known cirrhosis scheduled for EGD to assess for GEV.
Exclusion Criteria for Aim 2-4:
• Contraindications to MRI
• Recent treatment (< 1 year) for varices
• recent (< 1 year) GEV bleeding
• Known occlusive thrombus in portal vein; splenic vein, or superior mesenteric vein
• Large hepatocellular carcinoma (HCC) with known PV involvement
• hypersensitivity reactions to both contrast agents
Expanded Access Protocol (EAP) for Subjects Receiving Idecabtagene Vicleucel That is Nonconforming for Commercial Release
This study is designed to evaluate the safety and efficacy of nonconforming idecabtagene
vicleucel (ide-cel) in subjects with multiple myeloma per the approved prescribing
information. This is an expanded access protocol (EAP) to be conducted at Risk Evaluation and
Mitigation Strategies (REMS) qualified sites approved for commercial administration of
idecabtagene vicleucel and where the EAP is authorized to be conducted for use of
nonconforming idecabtagene vicleucel.
Non-conforming idecabtagene vicluecel is idecabtagene vicleucel that does not meet commercial
release specifications but may be acceptable for use as an investigational product in the
Expanded Access Protocol setting.
Natalie Callander, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04771078
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Subject has multiple myeloma, 18 years of age or older and subject or legally
authorized representative is able to sign the informed consent form.
2. Subject had a subject-specific batch of idecabtagene vicluecel manufactured intended
for commercial treatment; however, the final manufactured product was nonconforming
and did not meet commercial release criteria. The Sponsor has determined that the
nonconforming idecabtagene vicleucel may be released for use under the Expanded Access
Protocol.
3. Remanufacturing is deemed not feasible or clinically inappropriate per assessment of
the treating physician in discussion with the subject.
4. Subject is clinically stable, has recovered from any prior toxicities prior to
receiving lymphodepleting chemotherapy, and has adequate bone marrow function to
receive lymphodepleting chemotherapy
5. Females of childbearing potential must:
1. Have a negative pregnancy test as verified by the treating physician within 7
days prior to the first dose of lymphodepleting chemotherapy following
institutional testing methodology practices. This applies even if the subject
practices true abstinence from heterosexual contact.
2. Either commit to true abstinence from heterosexual contact or agree to use, and
be able to comply with, effective contraception without interruption.
Contraception methods must include 1 highly effective method from screening until
at least 12 months after the lymphodepleting chemotherapy.
3. Agree to abstain from breastfeeding during study participation and for at least
12 months following lymphodepleting chemotherapy.
4. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception and the abstaining from breastfeeding following
treatment with nonconforming idecabtagene vicluecel. Any decision regarding
contraception and breastfeeding after infusion should be discussed with the
treating physician.
6. Male subjects must:
1. Practice true abstinence or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential for at least 12 months
after lymphodepleting chemotherapy even if the subject has undergone a successful
vasectomy.
2. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception following treatment with nonconforming idecabtagene
vicluecel. Any decision regarding contraception after infusion should be
discussed with the treating physician.
Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells for
usage in other individuals for at least 1 year following lymphodepleting chemotherapy.
There are insufficient exposure data to provide any recommendation concerning the duration
of refraining from tissue donation following treatment with nonconforming idecabtagene
vicluecel. Therefore, participants treated with nonconforming idecabtagene vicluecel should
not donate blood, organs, tissues, and cells for transplantation.
Exclusion Criteria:
1. Subject has a hypersensitivity to the active substance or to any of the excipients.
2. Subject should not experience a significant worsening in clinical status that would,
in the opinion of the treating physician, either increase the risk of AEs associated
with lymphodepleting chemotherapy or exclude them from treatment with nonconforming
idecabtagene vicluecel.
3. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness, sociologic or geographic condition that would prevent the subject from
participating in the Expanded Access Protocol, complying with protocol requirements or
confound the ability to interpret the data in the Investigator's judgement.
4. Subject has any condition and/or laboratory abnormality that places the subject at
unacceptable risk if he/she were to participate in the Expanded Access Protocol based
on the Investigator's judgement.
5. Pregnant or nursing women or has intention of becoming pregnant during the study.
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with
selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib
alone in treating children and young adults with low-grade glioma (a common type of brain
cancer) that has come back after prior treatment (recurrent) or does not respond to therapy
(progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells
grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill
cancer cells. Giving selumetinib in combination with vinblastine may work better than
selumetinib alone in treating recurrent or progressive low-grade glioma.
Kenneth Desantes, M.D.
All
2 Years to 25 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04576117
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Feasibility phase: patients must be >= 2 years and =< 21 years of age at the time of
enrollment
• Efficacy phase: patients must be >= 2 years and =< 25 years of age at the time of
enrollment
• All patients > 21 years of age at the time of enrollment must have had initial
diagnosis of low-grade glioma by 21 years of age
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have eligibility confirmed by rapid central pathology and central
molecular screening reviews performed on APEC14B1
• Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC)
low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
• Patients must have progressive or recurrent LGG. Note: Biopsy may be at either
initial diagnosis or recurrence
• Patients must have measurable disease, defined as having a two-dimensional
measurable tumor volume of >= 1 cm^2
• Tumor size will be measured to include both solid and cystic components of
the tumor (whether or not tumor is enhancing) + fluid attenuated inversion
recovery (FLAIR) signal
• Eligible histologies will include all tumors considered low-grade glioma or
low-grade astrocytoma (World Health Organization [WHO] grade 1 and II) by the WHO
Classification of Tumors of the Central Nervous System •4th Edition Revised,
with the exception of subependymal giant cell astrocytoma
• Patients with metastatic disease or multiple independent primary LGGs are
eligible
• Patients must be progressive or recurrent after having been treated with at least one
prior tumor-directed therapy before enrollment
• Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry
onto this study (4 weeks if prior nitrosourea);
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy
with a biologic agent;
• Radiation therapy (RT): >= 2 weeks (wks) for local palliative RT (small port); >=
6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of
pelvis; >= 6 wks must have elapsed if other substantial bone marrow (BM)
radiation;
• 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;
• MEK inhibitor or vinblastine: Must not have received treatment with a MEK
inhibitor or vinblastine within 6 months of study enrollment
• 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 (within 7 days
prior to enrollment):
• 2 to < 6 years: 0.8 mg/dL (male) 0.8 mg/dL (female)
• 6 to < 10 years: 1 mg/dL (male) 1 mg/dL (female)
• 10 to < 13 years: 1.2 mg/dL (male) 1.2 mg/dL (female)
• 13 to < 16 years: 1.5 mg/dL (male) 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male) 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L
(within 7 days prior to enrollment)
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• Albumin >= 2 g/L (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT interval (QTc interval) =< 450 msec by electrocardiogram (EKG) (within 4
weeks prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should not have
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Stable neurological examination for >= 1 week
• HYPERTENSION:
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile
for age, height, and gender at the time of enrollment (with or without the use of
anti-hypertensive medications);
• Patients >= 18 years of age must have a blood pressure =< 130/80 mmHg at the time
of enrollment (with or without the use of anti-hypertensive medications)
• Note for patients of all ages: Adequate blood pressure can be achieved using
medication for the treatment of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site[s] of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• Note: If surgical resection or biopsy is performed at the time of progression or
recurrence, a post-operative MRI is required
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
Exclusion Criteria:
• Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following
exceptions:
• Patients must not have had progressive disease while on therapy with vinblastine
or a MEK inhibitor;
• Patients must not have discontinued vinblastine or selumetinib due to toxicity
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients with diffuse intrinsic pontine tumors as seen on MRI (> 2/3 of pons
involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
• Patients may not be receiving any other investigational agents
• Patients must not have known hypersensitivity to selumetinib, vinblastine, or similar
compounds
• CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong
inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
• Patients with any serious medical or psychiatric illness/condition, including
substance use disorders or ophthalmological conditions, likely in the judgment of the
investigator to interfere or limit compliance with study requirements/treatment
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• PRE-EXISTING CONDITIONS (CARDIAC):
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented;
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current
cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or upper limit of normal (ULN) adjusted by age are
not eligible
• Any multivitamin containing vitamin E must be stopped prior to study enrollment even
if it contains less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy,
placement of a vascular access device or cerebrospinal fluid (CSF) diverting procedure
such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt
• Note: Patients must have healed from any prior surgery
• Patients who have an uncontrolled infection are not eligible
• Female patients who are pregnant are not eligible 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 and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• 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
Recurrent Low Grade Astrocytoma, Recurrent WHO Grade 2 Glioma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Refractory WHO Grade 1 Glioma, Brain and Nervous System, Brain/Central Nervous System
This is an expanded access protocol that will be conducted at sites qualified and approved to
treat subjects with lisocabtagene maraleucel. Sometimes when lisocabtagene maraleucel is
manufactured the drug does not pass all the testing results to be called lisocabtagene
maraleucel. When this happens the drug is called nonconforming lisocabtagene maraleucel. The
expanded access protocol will be used to allow subjects to receive nonconforming
lisocabtagene maraleucel only if the potential benefit is better than the potential risk.
This expanded access protocol is restricted to those subjects who were prescribed
lisocabtagene maraleucel as part of their routine care.
Subjects will first receive a lymphodepleting chemotherapy regimen and then be treated with
nonconforming lisocabtagene maraleucel as the treatment plan.
Vaishalee Kenkre, MD
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04400591
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Subject and/or LAR must understand and voluntarily sign an informed consent form prior
to any study-related assessments/procedures being conducted.
2. Subject has relapsed and/or refractory large B-cell lymphoma and is, per the treating
physician assessment, eligible for treatment with lisocabtagene maraleucel per the
approved prescribing information.
3. Subject is ≥ 18 years of age at the time of signing the informed consent form.
4. Subject had a specific batch of lisocabtagene maraleucel manufactured intended for
commercial treatment; however, the final manufactured product did not meet commercial
release criteria.
5. Remanufacturing (eg, repeat leukapheresis and manufacturing) is deemed not feasible or
clinically inappropriate per assessment of the treating physician in discussion with
the subject.
6. Subject is clinically stable, has recovered from any toxicities prior to receiving
lymphodepleting chemotherapy, and has adequate bone marrow function to receive
lymphodepleting chemotherapy. The treating physician is advised to contact Medical
Monitor in the event there is any concern regarding administration of lymphodepleting
chemotherapy.
7. Females of childbearing potential must:
1. Have a negative pregnancy test as verified by the treating physician within 7
days prior to the first dose of lymphodepleting chemotherapy following
institutional testing methodology practices. This applies even if the subject
practices true abstinence from heterosexual contact.
2. Either commit to true abstinence from heterosexual contact or agree to use, and
be able to comply with, effective contraception without interruption.
Contraception methods must include 1 highly effective method from screening until
at least 12 months after the nonconforming lisocabtagene maraleucel
administration.
3. Agree to abstain from breastfeeding during study participation and for at least
12 months following nonconforming lisocabtagene maraleucel administration.
4. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception and the abstaining from breastfeeding following
treatment with lisocabtagene maraleucel. Any decision regarding contraception and
breastfeeding after infusion should be discussed with the treating physician.
8. Male subjects must:
1. Practice true abstinence or agree to use a condom during sexual contact with a
pregnant female or a female of childbearing potential for at least 12 months
after nonconforming lisocabtagene maraleucel administration even if the subject
has undergone a successful vasectomy.
2. There are insufficient exposure data to provide any recommendation concerning the
duration of contraception following treatment with lisocabtagene maraleucel. Any
decision regarding contraception after infusion should be discussed with the
treating physician
9. Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells
for usage in other individuals for at least 1 year following nonconforming
lisocabtagene maraleucel administration.
Exclusion Criteria:
1. Subject has a hypersensitivity to the active substance or to any of the excipients.
2. Subject should not experience a significant worsening in clinical status that would,
in the opinion of the treating physician, either increase the risk of adverse events
associated with lymphodepleting chemotherapy, or exclude them from treatment with
nonconforming lisocabtagene maraleucel.
3. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness, sociologic or geographic condition that would prevent the subject from
participating in the Expanded Access Protocol complying with protocol requirements in
the Investigator's judgement.
4. Subject has any condition and/or laboratory abnormality that places the subject at
unacceptable risk if he/she were to participate in the Expanded Access Protocol based
on the Investigator's judgement
5. Pregnant or nursing women or has intention of becoming pregnant during the study.
6. Subjects with central nervous system (CNS)-only involvement by malignancy (note:
subjects with secondary CNS involvement are allowed on study).
7. Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
infection at the time of pretreatment evaluation
8. Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite
appropriate antibiotics or other treatment at the time of nonconforming lisocabtagene
maraleucel administration.
9. Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD)
10. Use of the following:
1. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
equivalent) within 72 hours prior to nonconforming lisocabtagene maraleucel
administration. Physiologic replacement, topical, and inhaled steroids are
permitted.
2. Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300
mg/m2)given after leukapheresis to maintain disease control must be stopped ≥ 7
days prior to lymphodepleting chemotherapy.
3. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below)
within 1 week of LD chemotherapy. Oral chemotherapeutic agents, including
lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed
prior to lymphodepleting chemotherapy.
4. Donor lymphocyte infusions within 6 weeks of nonconforming lisocabtagene
maraleucel administration.
Non-Hodgkin's Lymphoma, Lymphoma, Lymphoma, Large B-Cell, Diffuse
DNA-Guided Second Line Adjuvant Therapy For High Residual Risk, Stage II-III, Hormone Receptor Positive, HER2 Negative Breast Cancer (DARE)
A randomized, Phase II trial of circulating tumor DNA-guided second line Adjuvant therapy for
high Residual risk, stage II-III, Estrogen Receptor positive, HER-2 negative breast cancer
(DARE)
Mark Burkard, MD, PhD
All
Not specified
Phase 2
This study is NOT accepting healthy volunteers
NCT04567420
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
•4.1.1. Stage II or III, HER2 negative, ER positive invasive breast cancer in male or
female patients. For this study, ER positivity is defined as equal to or greater than 10%
ER positivity by immunohistochemistry, regardless of progesterone receptor (PR) status.
Patients with PR positive but ER negative cancer are not eligible. HER2 negative status is
defined as per the ASCO/CAP 2018 practice guidelines.
(i) if patients have synchronous bilateral ER+ breast cancer tissue from both sites should
be submitted to Natera to perform ctDNA testing.
(ii) patients with multifocal/multicentric tumors are eligible and the largest focus of
cancer should be submitted for testing. All tumors must meet pathological criteria for
HER2-and ER+ status.
(iii) For. patients who received neoadjuvant therapy and have discordant ER and HER2
results between the diagnostic biopsy (pre-treatment) and surgical pathology (post
neoadjuvant therapy), the ER+ and HER2- status of the post-treatment specimen determine
eligibility.
4.1.2. Currently taking an aromatase inhibitor, or tamoxifen, as adjuvant endocrine therapy
and have completed at least 6 months (i.e. 24 weeks), but no more than 7 years with 3 more
years planned, of endocrine therapy. Patients may register for the screening phase of the
study within the first 6 months of adjuvant endocrine therapy but the first ctDNA testing
must occur at, or after, 6 months of endocrine therapy.
(i) Adjuvant bisphosphonate therapy is allowed. (ii) LHRH analogues are required for
premenopausal patients randomized to receive fulvestrant.
4.1.3. Clinical and pathological high risk for recurrence defined as any one of the
following: (i) At least a 15% predicted risk of death within 10 years using ePREDICT V2.1
(https://breast.predict.nhs.uk/tool), or (ii) At least 15% or greater risk of distant
metastasis within 10 years using RSPC,
(https://tools.genomichealth.com/Tools/RSPCTool.aspx), or (iii) At least 15% or greater
risk of distant metastasis within 10 years CTS5 (https://www.cts5-calculator.com) for
patients who have completed a minimum of 4 years of adjuvant endocrine therapy, or (iv)
Tumor size > 5 cm, regardless of lymph node status, or (v) 1-3 involved axillary lymph
nodes and at least one of the following;
• Tumor size > 3 cm,
• High histological grade (e.g. grade 3).
• High genomic risk defined as Oncotype Dx Recurrence Score >26, EndoPredict score >4,
Prosigna risk of recurrence score ≥ 60, or Mammaprint high risk.
(vi) Patients who have received pre-operative (neoadjuvant) chemotherapy must have either:
• greater than or equal to 3 cm invasive residual cancer regardless of nodal status AND
grade 3 disease or RS>26/MammPrint High/Prosigna high/Endopredict high status, or
• greater than or equal to 1 cm invasive residual cancer (ypT1c) and at least 1 positive
lymph node (ypN+) AND grade 3 disease, or RS>26, or MammPrint High, or Endopredict
high or Prosigna high status.
4.1.4. Patients must have FFPE tissue from the primary tumor available for submission to
Natera to perform ctDNA assay (see Appendix B for tissue submission instructions).
4.1.5. Signed and dated informed consent, including willingness to be randomized to
standard of care versus fulvestrant + palbociclib.
4.2 Inclusion and exclusion criteria for treatment randomization
Inclusion criteria for randomization
4.2.1. ctDNA positivity by the Signatera assay, defined as 2 of the 16 cancer specific
markers positive in plasma.
4.2.2. Patients with positive Signatera results obtained in the context of commercial
testing, outside of the screening phase of this trial, are also eligible for randomization
if they meet other eligibility criteria.
4.2.3. No evidence of metastatic disease on CT scan of the chest, abdomen and pelvis.
• If imaging, after review with a radiologist, is low probability for metastatic
disease, patients may proceed to randomization.
• Patients with suspicious but inconclusive imaging results should undergo a diagnostic
biopsy, if biopsy is negative patients are eligible for randomization.
• Patients with positive imaging that is conclusive of metastatic disease, or with
biopsy proven metastatic disease, are not eligible for randomization.
4.2.4. Pre-menopausal women and male patients must be willing to use an adequate method of
contraception for the duration of trial treatment and for 4 additional weeks after
completion of treatment in the control arm, and for 2 years after the last dose of
fulvestrant, if randomized into the experimental arm.
Post-menopausal status is defined as:
• Documented bilateral oophorectomy.
• Age ≥ 60 years.
• Age < 60 years and amenorrhoeic for ≥ 12 consecutive months and FSH and estradiol
levels in the post-menopausal range according to the institutional reference range for
post-menopausal.
Adequate contraception is defined as ONE highly effective form (i.e. abstinence, surgical
sterilization through bilateral tubal ligation, vasectomy), or TWO effective forms (e.g.
non-hormonal IUD and condom / occlusive cap with spermicidal foam / gel / film / cream /
suppository).
•Abstinence is to be interpreted as "true abstinence" for heterosexual intercourse and
therefore, "periodic abstinence" (e.g. calendar, symptothermal, post-ovulation methods) and
withdrawal (coitus interruptus) are not considered highly effective.
Exclusion Criteria
4.1.5. Prior or current treatment with fulvestrant, or current treatment with a CDK4/6
inhibitor, or treatment in the prior 12 months, or participants in the PENELOPE and PALLAS
clinical trials.
4.1.6. Patients cannot start participation in another therapeutic clinical trial for breast
cancer after enrollment in this trial.
4.1.7. Patients with current or past invasive cancer, other than breast cancer are not
eligible, except:
• Adequately treated basal or squamous cell carcinoma of the skin are eligible.
• Cancer survivors of previously diagnosed invasive cancer, who were treated with a
curative intent, have no evidence of disease recurrence for 5 years or more, and are
considered low risk for future recurrence by the treating physician are also eligible.
4.1.8. Patients with a second HER2 positive or triple negative synchronous breast cancer
are not eligible.
Exclusion criteria for randomization
4.2.5. Patients with known contraindications to receive fulvestrant and palbociclib or
those who are unable to tolerate these drugs are not eligible.
• Absolute neutrophil count less than <1000/mm3;
4.2.6. Any concurrent severe and uncontrolled medical condition that would, in the
Investigator' opinion cause unacceptable safety risks or compromise compliance with the
protocol including but not limited to:
• Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral medication (e.g. Crohn's disease, ulcerative diseases,
uncontrolled chronic nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection).
• History of pneumonitis, interstitial lung disease or pulmonary fibrosis.
• Known history of Human Immunodeficiency Virus (HIV) (testing is not mandatory).
• Known active Hepatitis B or Hepatitis C (testing is not mandatory).
• Females who are pregnant or breastfeeding.
• History of bleeding diathesis (i.e. disseminated intravascular coagulation, clotting
factor deficiency) that preclude the IM injections of fulvestrant or LHRH agonist as
applicable.
4.2.7 Patients taking any CYPC3A4 strong inducers and inhibitors, that cannot be changed.
Additional Support Program Via Text Messaging and Telephone-Based Counseling for Breast Cancer Patients Receiving Hormonal Therapy
This phase III trial compares an additional support program (text message reminders and/or
telephone-based counseling) with usual care in making sure breast cancer patients take their
endocrine therapy medication as prescribed (medication adherence). Medication adherence is
how well patients take the medication as prescribed by their doctors, and good medical
adherence is when patients take medications correctly. Poor medication adherence has been
shown to be a serious barrier to effective treatment for hormone receptor positive breast
cancer patients. Adding text message reminders and/or telephone-based counseling to usual
care may increase the number of days that patients take their endocrine therapy medication as
prescribed.
Toby Campbell, MD
Female
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04379570
Show full eligibility criteria
Hide eligibility criteria
• Women with an initial pathologically confirmed diagnosis of stage I-III, hormone
receptor positive, HER2-neu negative, invasive breast cancer within 18 months prior to
enrollment
• Women who have undergone neo-adjuvant chemotherapy who have no residual invasive
disease post-surgery are eligible based on an initial pathologically confirmed
diagnosis
• Hormone receptor positive is defined as estrogen receptor (ER) and/or
progesterone receptor (PR) of > 1%
• HER2-neu negative is defined as 0-1+ by immunohistochemical (IHC) analysis, or
non-amplified by fluorescence in situ hybridization (FISH) analysis
• Patients must have received cancer-directed surgery, and/or completed all other
adjuvant therapy, except reconstruction
• Patients must have initiated an endocrine therapy drug within the 6 months prior to
registration, OR have received a prescription with stated intent to initiate within 6
weeks after registration
• No history of previous cancer as follows:
• Invasive or non-invasive breast cancer at any time
• Non-breast cancer, within the past 5 years, excluding non-melanoma skin cancer
• Patients must be willing to use a smart phone for study activities
• Patient is NOT to be deemed ineligible during the recruitment process if they do
not have a smart phone
• If a participant does not own a smart phone or has limited data or texting
capabilities or their smart phone cannot support the Alliance electronic patient
reported outcomes (ePRO) survey application (app), a smart phone and service can
be provided to the participant at no cost through the Ohio State University (OSU)
partnership with Verizon Wireless for the duration of the study activities
• The CRP is ONLY to discuss this option with those patients who self-identify a
phone-related barrier to participation, including: lack of a smart phone,
insufficient phone plan (minutes/text/data), or a smart phone incompatible with
the Alliance ePRO app
• For OSU -provided phones, charges will be paid by the grant through the
intervention period. At the end of the 12-month intervention period, patients
will be responsible for paying monthly fees, if continued service is desired. The
physical phones will belong to the patients at the end of their study activities
• Patients must be willing to use a Pillsy medication event monitoring system for the
duration of study participation
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and read English
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, HER2 Negative Breast Carcinoma, Hormone Receptor Positive Breast Carcinoma, Invasive Breast Carcinoma, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Breast
*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.