Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate progression-free survival (PFS) by blinded independent central review (BICR) in patients treated with intermittent regimen of relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel monotherapy.

Detailed Description
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As there are no currently approved therapies or effective standard of care for heavily pretreated patients with ovarian cancer who have exhausted single-agent chemotherapy and/or bevacizumab, the combination of intermittently administered relacorilant and nab-paclitaxel may demonstrate a substantial improvement without increased toxicity compared with nab-paclitaxel. Patients will receive study treatment until confirmed progressive disease (PD) or unacceptable toxicity. All patients will be followed for the collection of study endpoints, inclusive of disease progression and survival.

Official Title
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A Phase 3 Study of Relacorilant in Combination With Nab-Paclitaxel Versus Nab-Paclitaxel Monotherapy in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer (ROSELLA)

Conditions
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Ovarian Neoplasm, Fallopian Tube Neoplasms, Peritoneal Neoplasms

Intervention / Treatment
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* Drug: Nab-paclitaxel 80 mg/m^2
* Drug: Relacorilant 150 mg once daily (QD)
* Drug: Nab-paclitaxel 100 mg/m^2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to study-specific screening procedures. Confirmed histologic diagnosis of high-grade (Grade 3) serous, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. Patients must have platinum-resistant disease (defined as RECIST v1.1 defined progression <6 months from completion of a platinum-containing therapy). Must consent to provide archival tumor-tissue block or slides. Patients may consent to an optional tumor biopsy if archival tumor is unavailable. Has a life expectancy of ≥3 months. At least one lesion that meets the definition of measurable disease by RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Able to comply with protocol requirements. Able to swallow and retain oral medication and does not have uncontrolled emesis. Received at least 1 but ≤3 lines of prior systemic anticancer therapy and at least 1 prior line of platinum therapy and prior treatment with bevacizumab is required. Has 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 in context of liver metastases, Total bilirubin ≤1.5 × ULN, and Albumin ≥3 g/dL, and creatinine clearance >40 mL/min/1.73 m^2 (measured or estimated). Negative pregnancy test for patients of childbearing potential; patients of childbearing potential must agree to use highly effective contraceptive method(s); hormonal contraceptives are not allowed. Coronavirus disease (COVID-19) approved vaccines are accepted concomitant medications when recommended by the Investigator. Exclusion Criteria: Has clinically relevant toxicity from prior systemic anticancer therapies or radiotherapy that has not resolved to ≤Grade 1 prior to randomization. Has had any major surgery within 4 weeks prior to randomization. Has low-grade endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of these histologies, or low-grade or borderline ovarian tumor. Has primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤1 month of the last dose of first-line platinum-containing chemotherapy. Has not received prior bevacizumab treatment. Has been treated with the following prior to randomization: chemotherapy, immunotherapy, investigational agent treatments for disease under study within 28 days before first dose of study drug, radiotherapy not completed at least 2 weeks prior to first dose of study drug, hormonal anticancer therapies within 7 days of first dose of study drug, and systemic, inhaled, or prescription strength topical corticosteroids within 21 days of first dose of study drug. Has received wide-field radiation to more than 25% of marrow-bearing areas. Has toxicities of prior therapies that have not resolved the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, ≤Grade 1. Requires treatment with chronic or frequently used oral corticosteroids for medical conditions or illnesses. Has a history of severe hypersensitivity or severe reaction to any of the study drugs. Is receiving concurrent treatment with mifepristone or other glucocorticoid receptor (GR) modulators. Has peripheral neuropathy from any cause >Grade 1. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial, starting with the screening visit through at least 1 month after the last dose of relacorilant, or 6 months after the last dose of nab-paclitaxel whichever is the longest. Has clinically significant uncontrolled condition(s) or condition which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient's safety or participation. Has current chronic/active infection with human immunodeficiency virus or current chronic/active infection with hepatitis C virus or hepatitis B virus. Has any untreated or symptomatic central nervous system (CNS) metastases. Patients with a history of other malignancy within 3 years prior to randomization Is taking a concomitant medication that is a strong cytochrome P450 (CYP)3A inhibitor or strong CYP3A inducer, or that is a substrate of CYP3A with a narrow therapeutic window. Concurrent treatment on other investigational treatment studies for the treatment of ovarian, fallopian tube, or primary peritoneal cancer. Has received a live vaccine within 30 days of prior to the study start date.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nab-paclitaxel 80 mg/m^2 with Relacorilant 150 mg<br>Patients receive nab-paclitaxel 80 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle in combination with intermittent relacorilant (150 mg relacorilant once daily on the day before, the day of, and the day after nab-paclitaxel), administered orally under fed conditions. Relacorilant will not be administered on Cycle 1 Day -1. | Drug: Nab-paclitaxel 80 mg/m^2<br>* Nab-paclitaxel is administered as intravenous (IV) infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle.<br>Drug: Relacorilant 150 mg once daily (QD)<br>* Relacorilant is administered as capsules for oral dosing.<br>|
| Active Comparator: Nab-paclitaxel 100 mg/m^2<br>Patients receive nab-paclitaxel 100 mg/m^2 on Days 1, 8, and 15 of each 28-day cycle. | Drug: Nab-paclitaxel 100 mg/m^2<br>* Nab-paclitaxel is administered as IV infusion on Day 1, 8, and 15 of each 28-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival as Assessed by BICR | Time from randomization until the time of first documented progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause, whichever occurs first | Up to 24 months from enrollment of the last patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from randomization to death by any cause | Up to 24 months from enrollment of the last patient | 
| PFS as Assessed by the Investigator | Time from randomization until the time of first documented progressive disease (PD) by RECIST v1.1, or death due to any cause, whichever occurs first | Up to 24 months from enrollment of the last patient | 
| Objective Response as Assessed by BICR | Proportion of patients with measurable disease at baseline who attain CR or PR by RECIST v1.1. | Up to 24 months from enrollment of the last patient | 
| Best Overall Response as Assessed by BICR | Proportion of patients with measurable disease at baseline who attain CR or PR as best response by RECIST v1.1. | Up to 24 months from enrollment of the last patient | 
| Duration of Response as Assessed by BICR | Time from when response (CR or PR per RECIST v1.1) is first documented to first objectively documented PD or death (whichever occurs first) | Up to 24 months from enrollment of the last patient | 
| Clinical benefit rate as assessed by BICR | Proportion of patients who attain CR, PR, or stable disease (SD) per RECIST v1.1. | 24 weeks | 
| Cancer Antigen (CA)-125 Response | Cancer antigen (CA)-125 response will be assessed per Gynecologic Cancer Intergroup (GCIG) criteria defined as ≥50% reduction in CA-125 from a pre-treatment sample and maintained for ≥28 days in patients with a pretreatment sample that is at least twice the upper limit of the reference range within 2 weeks before starting the treatment. In addition, patients who have a CA-125 response and whose CA-125 level falls to within the reference range will be classified as CA-125 complete responders. | Up to 24 months from enrollment of the last patient | 
| Combined Response According to RECIST v1.1 and GCIG Criteria | Combined response will be assessed for PD per RECIST v1.1 and for CA-125 response per GCIG criteria | Up to 24 months from enrollment of the last patient |