Overview
This is a Phase 2, single-arm, open-label study to evaluate efficacy and safety of intermittent dosing of relacorilant in combination with nab-paclitaxel and bevacizumab in patients with ovarian cancer.
Description
Study treatment will be comprised of relacorilant, combined with nab-paclitaxel, and bevacizumab and will begin on Cycle 1 Day 1 (C1D1). Each patient will receive relacorilant 150 mg administered orally under fed conditions, once daily for 3 consecutive days on the day before, the day of, and the day after nab-paclitaxel infusion, in combination with nab-paclitaxel (80 mg/m^2 intravenous [IV]) administered on Days 1, 8, and 15 of each 28-day cycle. Bevacizumab (10 mg/kg IV once every 2 weeks [Q2W]) will be administered on Days 1 and 15 of each 28-day cycle. Patients will receive study treatment until they reach progressive disease, experience unmanageable toxicity, or until other discontinuation criteria are met. Patients will be monitored for treatment efficacy, safety, and tolerability.
Eligibility
Inclusion Criteria:
- Histologic diagnosis of high-grade serous/endometrioid, epithelial ovarian, primary peritoneal, or fallopian-tube carcinoma.
- Platinum-resistant disease (defined as progression <183 days from the last dose of platinum).
- At least 1 measurable (target) lesion per RECIST version 1.1.
- Life expectancy of ≥3 months.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Able to swallow and retain oral medication and does not have uncontrolled emesis.
- 1 to 3 lines of prior systemic anticancer therapy for ovarian cancer.
- ≥1 prior line of platinum-based therapy.
- Prior treatment with bevacizumab allowed.
- Adequate organ function meeting the following laboratory-test criteria:
- Absolute neutrophil count (ANC) ≥1500 cells/mm^3.
- Platelet count ≥100,000/mm^3.
- Hemoglobin ≥9 g/dL.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN if liver metastases.
- Total bilirubin ≤1.5 × ULN.
- Albumin ≥2.5 g/dL.
- Calculated creatinine clearance ≥35 mL/min.
- Urine protein <2+ by dipstick; if ≥2+, 24-hour urine <1 g of protein.
- Negative pregnancy test for patients of childbearing potential.
Exclusion Criteria:
- Has progressed while receiving weekly (every week or 3 out of 4 weeks) paclitaxel or nab-paclitaxel in the platinum-resistant ovarian cancer (PROC) setting.
- Prior anticancer therapy related toxicities not resolved to grade ≤1.
- Any surgery within 4 weeks prior to enrollment.
- Prior treatment as follows:
- Chemotherapy, immunotherapy, investigational agent etc. within 5 times the half-life of the prior therapy, or 28 days if 5 times the half-life of the prior therapy is >28 days, before the first dose of study treatment.
- Radiotherapy not completed ≤2 weeks prior to first dose of study treatment.
- Hormonal anticancer therapies within 7 days of first dose of study treatment.
- Corticosteroids used within a period equivalent to 5 times the half-life of the corticosteroid prior to first dose of study treatment.
- Wide-field radiation to more than 25% of marrow-bearing areas.
- Medical conditions requiring chronic or frequent treatment with corticosteroids.
- Concurrent treatment with mifepristone or other glucocorticoid receptor modulators.
- Peripheral neuropathy from any cause >Grade 1.
- Hypertension: ≥150 mm Hg systolic or ≥100 mm Hg diastolic.
- Uncontrolled condition(s) which, may confound the results of the trial or interfere with the patient's safety or participation, including unstable angina, myocardial infarction within 6 months prior to the first dose of study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication, severe/advancing cirrhosis, active infectious disease requiring IV therapy within 2 weeks prior to the first dose of study treatment, gastric-outlet obstruction, acute renal failure, known psychiatric disorder that would interfere with trial compliance.
- Bowel obstruction ≤12 weeks prior to study entry.
- Ascites or pleural effusions requiring therapeutic paracentesis or thoracentesis within the 30 days prior to study entry or anticipated within 30 days of C1D1.
- Non-healing wound, ulcer, or bone fracture.
- History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to C1D1.
- Evidence of recto-sigmoid involvement by ovarian cancer.
- Anticoagulants or thrombolytic agents use for therapeutic purpose within 10 days prior to study treatment start.
- Active infection with HIV, hepatitis C or hepatitis B virus.
- Untreated or symptomatic central nervous system metastases.
- History of other malignancy within 3 years prior to enrollment.
- Has received a live vaccine within 30 days prior to the study start date.