This is a Phase 2, open-label, randomized, 3-arm study to evaluate progression-free survival (PFS) in patients with recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer treated with intermittent or continuous regimens of relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel alone.
Relacorilant is a small molecule antagonist of the glucocorticoid receptor (GR). The goals of this study are to evaluate the efficacy of relacorilant either administered daily (continuous) or on the day prior, the day of, and the day after chemotherapy (intermittent) in combination with nab-paclitaxel in the treatment of platinum-resistant ovarian, fallopian tube, or primary peritoneal cancers compared with nab-paclitaxel alone. The safety, pharmacokinetics (PK), and pharmacodynamic profile of relacorilant in combination with nab-paclitaxel will also be assessed. Eligible patients will be randomized 1:1:1 to one of the following three treatment arms. Patient randomization will be stratified by treatment-free interval from most recent taxane (relapsed within 6 months vs \>6 months) and presence of ascites (yes vs no). * Arm A (Continuous relacorilant): Relacorilant starting at 100 mg, administered orally, once daily every day in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. * Arm B (Intermittent relacorilant): Relacorilant 150 mg, administered orally, on the day before (excluding Cycle 1, Day -1), the day of, and the day after nab-paclitaxel, in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. * Arm C (Comparator): Nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle. Patients will remain on study treatment until reaching a protocol-defined event of disease progression (PD), experiencing unmanageable toxicity, or until other treatment discontinuation criteria are met. All patients will be followed for progression, subsequent therapies, and survival in the long-term follow-up phase. Patients in Arm C who experience unequivocal PD per RECIST v1.1 will be given the opportunity to receive relacorilant in combination with nab-paclitaxel after discussion with the Medical Monitor (Crossover patients).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
178
Relacorilant is supplied as capsules for oral dosing.
Nab-paclitaxel is administered as IV infusion over 30-40 minutes.
Site Reference ID/Investigator #004
Birmingham, Alabama, United States
Site Reference ID/Investigator #038
Scottsdale, Arizona, United States
Site Reference ID/Investigator #032
Denver, Colorado, United States
Site Reference ID/Investigator #001
Chicago, Illinois, United States
Site Reference ID/Investigator #106
Boston, Massachusetts, United States
Site Reference ID/Investigator #128
Boston, Massachusetts, United States
Site Reference ID/Investigator #051
New York, New York, United States
Site Reference ID/Investigator #169
New York, New York, United States
Site Reference ID/Investigator #170
New York, New York, United States
Site Reference ID/Investigator #127
Pittsburgh, Pennsylvania, United States
...and 14 more locations
Progression-free Survival (PFS)
To assess time from randomization until the date of first documented progressive disease (PD) by RECIST v1.1 (as determined by the Investigator at the local site), or death due to any cause, whichever occurs first.
Time frame: Baseline and up to 15 months
Objective Response Rate (ORR)
To assess the proportion of patients with measurable disease at Baseline who attain complete response (CR) or partial response (PR) by RECIST v1.1 (confirmation not required).
Time frame: Baseline and up to 15 months
Duration of Response (DOR)
To assess the time from when response (CR or PR) was first documented to the first objectively documented PD or death (whichever occurs first)
Time frame: From first documented response up to 12 months
Cancer Antigen 125 (CA-125) Response According to Gynecological Cancer Intergroup Criteria (GCIG)
To assess the overall CA-125 response per GCIG criteria. Response was defined as ≥50% reduction in CA-125 from a pre-treatment sample. Patients whose CA-125 levels fall within the reference range are classified as complete responders.
Time frame: Baseline and up to 15 months
Best Overall Response (BOR)
To assess the best response (CR, PR, stable disease \[SD\], or PD) recorded from the date of randomization until PD/recurrence (or death)
Time frame: Baseline and up to 15 months
PFS Rate at 6 and 12 Months
To assess the proportion of patients who have not progressed according to RECIST v1.1 criteria at 6 and 12 months. Values are Kaplan-Meier estimates of the patients progression-free at the time points specified.
Time frame: 6 and 12 months
PFS in Patients Who Cross Over to Continuous Treatment at Time of Initial PD
To assess the time from crossover Baseline (initial PD) until the earliest date of subsequent PD by RECIST v1.1, as determined by the Investigator at the local site, or death from any cause, whichever comes first.
Time frame: Crossover Baseline (Day 50) up to Day 272
ORR in Patients Who Cross Over to Continuous Treatment at Time of Initial PD
To assess the proportion of patients with measurable disease at the crossover Baseline who attain confirmed CR or PR by RECIST v1.1
Time frame: Crossover Baseline (Day 50) up to Day 272
DOR in Patients Who Cross Over to Continuous Treatment at Time of Initial PD
To assess the time from when the first objective response (CR or PR) in the crossover period to the first objectively documented subsequent PD, or death (whichever occurs first)
Time frame: From the time of objective response in the crossover period to the time of subsequent PD
BOR in Patients Who Cross Over to Continuous Treatment at Time of Initial PD
To assess the best overall response (CR, PR, SD, or PD) recorded in the crossover period
Time frame: Crossover Baseline (Day 50) up to Day 272
Overall Survival (OS)
To assess the time from randomization to death by any cause.
Time frame: Up to 31 months
Overall Response According to Combined RECIST v1.1 + GCIG Criteria
To assess the proportion of patients with measurable disease at Baseline who attain confirmed CR or PR by RECIST v1.1 and GCIG criteria. GCIG response was defined as ≥50% reduction in CA-125 from a pre-treatment sample.
Time frame: Baseline and up to 15 months
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