Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer
- Conditions
- Ovarian NeoplasmFallopian Tube NeoplasmsPeritoneal Neoplasms
- Interventions
- Drug: Nab-paclitaxel 80 mg/m^2Drug: Nab-paclitaxel 100 mg/m^2
- Registration Number
- NCT05257408
- Lead Sponsor
- Corcept Therapeutics
- Brief Summary
The primary objectives of this study are to evaluate progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS) (evaluated independently, as dual primary endpoints) in patients treated with intermittent regimen of Relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel monotherapy.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 381
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nab-paclitaxel 80 mg/m^2 with Relacorilant 150 mg Nab-paclitaxel 80 mg/m^2 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. Nab-paclitaxel 80 mg/m^2 with Relacorilant 150 mg Relacorilant 150 mg once daily (QD) 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. Nab-paclitaxel 100 mg/m^2 Nab-paclitaxel 100 mg/m^2 Patients receive nab-paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Progression-free Survival as Assessed by BICR Up to 24 months from enrollment of the last patient 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
Overall survival Up to 24 months from enrollment of the last patient Time from randomization to death by any cause
- Secondary Outcome Measures
Name Time Method Duration of Response as Assessed by BICR Up to 24 months from enrollment of the last patient Time from when response (CR or PR per RECIST v1.1) is first documented to first objectively documented PD or death (whichever occurs first)
PFS as Assessed by the Investigator Up to 24 months from enrollment of the last patient 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
Cancer Antigen (CA)-125 Response Up to 24 months from enrollment of the last patient 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.
Combined Response According to RECIST v1.1 and GCIG Criteria Up to 24 months from enrollment of the last patient Combined response will be assessed for PD per RECIST v1.1 and for CA-125 response per GCIG criteria
Objective Response as Assessed by BICR Up to 24 months from enrollment of the last patient Proportion of patients with measurable disease at baseline who attain CR or PR by RECIST v1.1.
Best Overall Response as Assessed by BICR Up to 24 months from enrollment of the last patient Proportion of patients with measurable disease at baseline who attain CR or PR as best response by RECIST v1.1.
Clinical benefit rate as assessed by BICR 24 weeks Proportion of patients who attain CR, PR, or stable disease (SD) per RECIST v1.1.
Trial Locations
- Locations (116)
Site 272
🇺🇸Atlanta, Georgia, United States
Site 339
🇺🇸Indianapolis, Indiana, United States
Site 127
🇺🇸Pittsburgh, Pennsylvania, United States
Site 341
🇵🇱Gdynia, Poland
Site 315
🇺🇸Evanston, Illinois, United States
Site 277
🇺🇸Tucson, Arizona, United States
Site 009
🇺🇸Atlanta, Georgia, United States
Site 150
🇺🇸Palo Alto, California, United States
Site 335
🇺🇸Miami Beach, Florida, United States
Site 316
🇺🇸Solvang, California, United States
Site 372
🇺🇸Gainesville, Georgia, United States
Site 200
🇺🇸Overland Park, Kansas, United States
Site 334
🇺🇸Overland Park, Kansas, United States
Site 292
🇺🇸Albuquerque, New Mexico, United States
Site 381
🇦🇷Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
Site 312
🇺🇸Bedford, Texas, United States
Site 128
🇺🇸Boston, Massachusetts, United States
Site 314
🇺🇸Hinsdale, Illinois, United States
Site 326
🇧🇪Charleroi, Belgium
Site 348
🇭🇺Győr, Hungary
Site 117
🇨🇦Toronto, Ontario, Canada
Site 426
🇦🇺St. Leonards, New South Wales, Australia
Site 306
🇫🇷Lille, France
Site 288
🇺🇸New Brunswick, New Jersey, United States
Site 414
🇦🇺Melbourne, Victoria, Australia
Site 109
🇧🇪Brussels, Belgium
Site 290
🇭🇺Debrecen, Hungary
Site 300
🇺🇸Norfolk, Virginia, United States
Site 419
🇦🇺Melbourne, Victoria, Australia
Site 413
🇧🇷São Paulo, Brazil
Site 310
🇫🇷Nice, France
Site 424
🇧🇷Brasília, Brasília - DF, Brazil
Site 328
🇧🇪Aalst, Belgium
Site 374
🇧🇷São Paulo, Brazil
Site 337
🇺🇸Bethlehem, Pennsylvania, United States
Site 391
🇦🇷Rosario, Santa Fe, Argentina
Site 301
🇺🇸The Woodlands, Texas, United States
Site 389
🇧🇷São Paulo, Brazil
Site 108
🇧🇪Leuven, Belgium
Site 320
🇮🇹Legnago, Italy
Site 319
🇮🇹Treviso, Italy
Site 273
🇨🇦Montréal, Quebec, Canada
Site 395
🇦🇷Ciudad de Cordoba, Cordoba, Argentina
Site 421
🇧🇷Porto Alegre, Brazil
Site 380
🇧🇷Rio De Janeiro, Brazil
Site 289
🇫🇷Paris, France
Site 399
🇰🇷Seoul, Korea, Republic of
Site 327
🇧🇪Liège, Belgium
Site 331
🇵🇱Poznań, Poland
Site 122
🇮🇹Milano, Italy
Site 124
🇮🇹Rome, Italy
Site 322
🇭🇺Budapest, Hungary
Site 402
🇰🇷Seoul, Korea, Republic of
Site 161
🇮🇹Roma, Italy
Site 307
🇫🇷Nancy, France
Site 295
🇮🇹Pavia, Italy
Site 330
🇪🇸Valencia, Spain
Site 345
🇬🇧Northwood, United Kingdom
Site 344
🇬🇧Manchester, United Kingdom
Site 400
🇰🇷Seoul, Korea, Republic of
Site 366
🇬🇧Cheltenham, United Kingdom
Site 367
🇬🇧Brighton, East Sussex, United Kingdom
Site 055
🇬🇧London, United Kingdom
Site 298
🇺🇸Cincinnati, Ohio, United States
Site 392
🇺🇸San Antonio, Texas, United States
Site 383
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Site 384
🇧🇷Salvador, Bahia, Brazil
Site 390
🇧🇷Natal, Rio Grande Do Norte, Brazil
Site 318
🇺🇸Phoenix, Arizona, United States
Site 281
🇺🇸Nashville, Tennessee, United States
Site 280
🇺🇸Portland, Oregon, United States
Site 317
🇺🇸Portland, Oregon, United States
Site 293
🇮🇹Torino, Italy
Site 121
🇺🇸Milwaukee, Wisconsin, United States
Site 398
🇰🇷Seoul, Korea, Republic of
Site 409
🇰🇷Seoul, Korea, Republic of
Site 350
🇺🇸Irvine, California, United States
Site 364
🇺🇸La Jolla, California, United States
Site 278
🇺🇸San Francisco, California, United States
Site 042
🇺🇸Weston, Florida, United States
Site 014
🇺🇸San Francisco, California, United States
Site 291
🇺🇸Savannah, Georgia, United States
Site 049
🇺🇸Portland, Oregon, United States
Site 346
🇺🇸Urbana, Illinois, United States
Site 275
🇺🇸Flushing, New York, United States
Site 304
🇺🇸Cincinnati, Ohio, United States
Site 276
🇺🇸Rapid City, South Dakota, United States
Site 368
🇺🇸Germantown, Tennessee, United States
Site 297
🇺🇸Fort Worth, Texas, United States
Site 417
🇦🇺Benowa, Queensland, Australia
Site 393
🇦🇷Caba, Buenos Aires, Argentina
Site 415
🇦🇷Ciudad de Cordoba, Cordoba, Argentina
Site 401
🇦🇷Ciudad de Cordoba, Cordoba, Argentina
Site 404
🇦🇷Ciudad de Mendoza, Mendoza, Argentina
Site 382
🇧🇷Fortaleza, Ceara, Brazil
Site 412
🇦🇷Rosario, Santa Fe, Argentina
Site 325
🇧🇪Hasselt, Belgium
Site 376
🇧🇷São Paulo, Brazil
Site 001
🇧🇷São Paulo, Brazil
Site 347
🇫🇷Montpellier, France
Site 323
🇫🇷Plérin, France
Site 080
🇮🇱Jerusalem, Israel
Site 321
🇮🇹Catania, Italy
Site 309
🇮🇱Haifa, Israel
Site 203
🇮🇱Tel Aviv, Israel
Site 397
🇰🇷Gyeonggi-do, Korea, Republic of
Site 403
🇰🇷Seoul, Korea, Republic of
Site 349
🇪🇸Badalona, Spain
Site 396
🇰🇷Seoul, Korea, Republic of
Site 329
🇵🇱Siedlce, Poland
Site 351
🇬🇧Taunton, Somerset, United Kingdom
Site 311
🇪🇸San Sebastián, Spain
Site 032
🇺🇸Aurora, Colorado, United States
Site 229
🇺🇸Austin, Texas, United States
Site 279
🇺🇸Louisville, Kentucky, United States
Site 365
🇺🇸Richmond, Virginia, United States