Status and phase
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About
The purpose of the study is to determine the optimal dose of CC-486 (oral azacitidine) in combination with pembrolizumab for the treatment of platinum-resistant/refractory Epithelial Ovarian Cancer (EOC).
Full description
This is an open-label, non-randomized, four-cohort study, in which intravenous pembrolizumab will be combined with 4 different schedules of administration of CC-486 (oral azacitidine), for the treatment of platinum-resistant/refractory (EOC). This is also a futility trial for the strategy to combine pembrolizumab and CC-486 in EOC. Eligible subjects will be treated in one of four cohorts of combined oral CC-486 and intravenous pembrolizumab (200 mg intravenous (IV) every 3 weeks in all cohorts) to evaluate the safety of each combination schedule and to have preliminary data on their efficacy. The primary objective is to establish the optimal dosing schedule for comparison with pembrolizumab alone.
Subjects will be assigned to a treatment cohort in the order they are enrolled in the study. In all subjects, tumor tissue will be obtained via image-guided core biopsy at study entry and 6 weeks after commencing treatment with CC-486. A cohort will remain open to accrual until five subjects treated on that cohort have completed two CC-486 cycles and have had the first post-baseline tumor burden assessment and both tumor biopsies performed and adequate paired tissue obtained. At least 5 evaluable subjects per cohort will be accrued over an estimated period of approximately 24 months.
Subjects will be treated in the assigned cohort until progressive disease based on Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST), unacceptable toxicity, consent withdrawal or the Investigator concludes that it is in the subject´s best interest to discontinue. Once 5 subjects in each cohort are considered evaluable for response, toxicity and treatment responses will be analyzed for each of the four cohorts and an optimal schedule will be selected.
This study includes mandatory tumor core biopsies for biomarkers research and mandatory whole blood sampling for deoxyribonucleic acid (DNA) methylation analyses.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Signed and dated informed consent document obtained prior to initiation of any study-specific procedure and treatment (by the subject or a legally acceptable representative as per the local regulations).
Women ≥ 18 years old
Histologically confirmed Epitheilial Ovarian Cancer (EOC), Fallopian Tube Cancer (FTC) or Primary Peritoneal Cancer (PPC).
Received debulking surgery and preoperative and/or postoperative platinum-based frontline chemotherapy (intravenous and/or intraperitoneal) for the treatment of EOC/FTC/PPC.
Documented platinum-resistant or platinum-refractory disease. Platinum-resistant disease is defined as progression within < 6 months from completion of a minimum of 4 platinum frontline therapy cycles in the pre or postoperative setting (the date should be calculated from the last administered dose of platinum agent). Platinum-refractory is defined as disease that has recurred/progressed while receiving platinum-based frontline therapy.
Measurable disease according to Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST)
Indication of systemic treatment for the relapsed EOC, FTC or PPC.
Subjects must have a tumor lesion that is amenable to an image-guided core biopsy and willingness to undergo two biopsies (baseline and 6 weeks after first dose of study treatment).
Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1.
Expected survival of more than 6 months.
Adequate organ function within 7 days prior to enrollment, as defined by the following criteria:
For women of childbearing potential, negative serum pregnancy test within 7 days of enrollment
Women of childbearing potential must agree to use acceptable methods of birth control starting with the screening visit and up to 120 days after the last dose of study treatment. Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
34 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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