A Phase 2, Randomized, Open-Label, 3-arm Study of Relacorilant in Combination With Nab-Paclitaxel for Patients With Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Relacorilant
- Conditions
- Recurrent Ovarian Cancer
- Sponsor
- Corcept Therapeutics
- Enrollment
- 178
- Locations
- 24
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
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.
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated Investigational Review Board/Independent Ethics Committee-approved informed consent form (ICF) prior to study-specific screening procedures.
- •Female patients aged ≥18 years old at time of consent
- •Histologic diagnosis of high grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma. Clear cell, mucinous and borderline histologic subtypes are excluded.
- •Received at least 1 line of therapy with evidence of cancer progression within 6 months after the last dose of platinum-based therapy (ie, having a platinum-free interval of ≤6 months \[platinum resistant\]), or progressive disease during or immediately after primary platinum-therapy, (ie, platinum refractory). Patients with primary platinum resistance (progression within 6 months of the last dose of first-line platinum-containing chemotherapy) are considered eligible.
- •Notes: For the calculation of the platinum-free interval, cancer progression must be defined by clear evidence of progression, such as radiographic progression per RECIST v1.
- •Calculating the platinum-free interval on the basis of increased Cancer Antigen (CA-125) is not allowed.
- •Measurable or non-measurable disease by RECIST v1.1:
- •Previously irradiated lesions are not allowed as measurable disease, unless there is documented evidence of progression in the lesions.
- •To be eligible with non-measurable disease, patients must have evaluable disease with CA 125 at least twice the upper limit of reference range (of CA-125 ≥70 U/mL), along with radiographically evaluable disease by computerized tomography (CT)/magnetic resonance imaging (MRI).
- •Availability and consent to provide tumor tissue for biomarker assays (archival or recent biopsy).
Exclusion Criteria
- •Clinically relevant toxicity from prior systemic anticancer therapies or radiotherapy that in the opinion of the Investigator has not resolved to Grade 1 or less prior to randomization.
- •Any major surgery within 4 weeks prior to randomization. If subject received major surgery including (curative or palliative surgery), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Treatment with the following prior to randomization:
- •Concurrent treatment with other anticancer therapy including other chemotherapy, immunotherapy, radiotherapy, chemoembolization, targeted therapy, an investigational agent or the non-approved use of a drug or device within 28 days before the first dose of study drug.
- •Hormonal anticancer therapies within 7 days of the first dose of study drug.
- •Systemic, inhaled, or prescription strength topical corticosteroids within 21 days of the first dose of study drug. Short courses (≤5 days) for non-cancer-related reasons are allowed if clinically required (such as prophylaxis for CT).
- •Received radiation to more than 25% of marrow-bearing areas.
- •Toxicities of prior therapies (except alopecia) that have not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 ≤Grade
- •Requirement for treatment with chronic or frequently used oral corticosteroids for medical conditions or illnesses (eg, rheumatoid arthritis, immunosuppression after organ transplantation).
- •History of severe hypersensitivity or severe reaction to either study drug.
Arms & Interventions
Arm A: Continuous Relacorilant Dosing
Patients will receive relacorilant 100 mg (titrated up to 150 mg after Cycle 1 or 2) once daily in combination with nab-paclitaxel 80 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Intervention: Relacorilant
Arm A: Continuous Relacorilant Dosing
Patients will receive relacorilant 100 mg (titrated up to 150 mg after Cycle 1 or 2) once daily in combination with nab-paclitaxel 80 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Intervention: Nab-paclitaxel
Arm B: Intermittent Relacorilant Dosing
Patients will receive relacorilant 150 mg on the day before (excluding Cycle 1, Day -1), the day of, and the day after nab-paclitaxel, in combination with nab-paclitaxel 80 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Intervention: Relacorilant
Arm B: Intermittent Relacorilant Dosing
Patients will receive relacorilant 150 mg on the day before (excluding Cycle 1, Day -1), the day of, and the day after nab-paclitaxel, in combination with nab-paclitaxel 80 mg/m\^2, on Days 1, 8, and 15 of each 28-day cycle.
Intervention: Nab-paclitaxel
Arm C: Nab-paclitaxel Comparator
Patients will receive nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle. Patients initially in Arm C who choose to cross over after disease progression will receive relacorilant 100 mg (titrated up to 150 mg) in combination with nab-paclitaxel 80 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle after cross over.
Intervention: Relacorilant
Arm C: Nab-paclitaxel Comparator
Patients will receive nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle. Patients initially in Arm C who choose to cross over after disease progression will receive relacorilant 100 mg (titrated up to 150 mg) in combination with nab-paclitaxel 80 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle after cross over.
Intervention: Nab-paclitaxel
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: Baseline and up to 15 months
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.
Secondary Outcomes
- Objective Response Rate (ORR)(Baseline and up to 15 months)
- Duration of Response (DOR)(From first documented response up to 12 months)
- Cancer Antigen 125 (CA-125) Response According to Gynecological Cancer Intergroup Criteria (GCIG)(Baseline and up to 15 months)
- Best Overall Response (BOR)(Baseline and up to 15 months)
- PFS Rate at 6 and 12 Months(6 and 12 months)
- PFS in Patients Who Cross Over to Continuous Treatment at Time of Initial PD(Crossover Baseline (Day 50) up to Day 272)
- ORR in Patients Who Cross Over to Continuous Treatment at Time of Initial PD(Crossover Baseline (Day 50) up to Day 272)
- DOR in Patients Who Cross Over to Continuous Treatment at Time of Initial PD(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(Crossover Baseline (Day 50) up to Day 272)
- Overall Survival (OS)(Up to 31 months)
- Overall Response According to Combined RECIST v1.1 + GCIG Criteria(Baseline and up to 15 months)