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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
CC-486 Intervention will depend on cohort enrolled in. 100 mg tablet
Pembrolizumab 200 mg IV every 21 days
UCLA
Los Angeles, California, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Number of Subjects With Grade 3, 4, or 5 Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Safety evaluation: number of subjects with grade 3, 4, or 5 adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency, severity and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.
Time frame: The average time period for patient participation was 30 weeks.
Number of Subjects With Immune-related Partial Response (irPR), Immune-related Complete Response (irCR), Immune-related Stable Disease (irSD), Immune-related Progressive Disease (irPD), and Immune-related Not Evaluable (irNE) as Assessed by irRECIST.
Efficacy evaluation: based on the Immune-related Objective Response Rate (irORR)/ Immune-related Disease Control Rate (irDCR) per Immune-Related Response Evaluation Criteria In Solid Tumor (irRECIST) criteria using the intent-to-treat (ITT) population (all patients who were enrolled in the study, regardless of whether they actually received study medication). The best overall response outcome (irCR/irPR/irSD/irPD/irNE) will be summarized and tabulated for ITT by cohort.
Time frame: The average time period for patient participation was 30 weeks.
Number of Subjects With Treatment Emergent Adverse Events Related to CC-486 as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
Safety evaluation: number of subjects with treatment emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.
Time frame: The average time period for patient participation was 30 weeks.
Number of Subjects With Treatment Emergent Adverse Events Related to Pembrolizumab as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
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Safety evaluation: number of subjects with treatment emergent adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. This is an assessment of the frequency and relationship to trial treatment of all adverse events that occurred while on trial. CTCAE is a standard classification and severity grading scale (from 1- mild to 5 - death) for adverse events in clinical trials and oncology settings.
Time frame: The average time period for patient participation was 30 weeks.