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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Fallopian Tube Neoplasms; Peritoneal Neoplasms; Ovarian Neoplasm
• Intervention / Treatment: Drug: Nab-paclitaxel 80 mg/m^2; Drug: Relacorilant 150 mg once daily (QD); Drug: Nab-paclitaxel 100 mg/m^2

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.

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: L. Dreiling, MD; Phone Number: (650) 327-3270; Email: ROSELLA556@corcept.com
• Study Contact Backup: Name: Sachin Pai, MD; Phone Number: (650) 688-2868; Email: ROSELLA556@corcept.com

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1280AEB
      • Site 393
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1426ANZ
      • Site 381
  • Cordoba
    • Ciudad de Cordoba, Cordoba, Argentina, X5004FHP
      • Site 415
    • Ciudad de Cordoba, Cordoba, Argentina, X5008 HHW
      • Site 401
    • Ciudad de Cordoba, Cordoba, Argentina, X5016
      • Site 395
  • Mendoza
    • Ciudad de Mendoza, Mendoza, Argentina, M5500AYB
      • Site 404
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Site 391
    • Rosario, Santa Fe, Argentina, S2000KDS
      • Site 412
• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Site 426
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Site 417
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Site 414
    • Melbourne, Victoria, Australia, 3128
      • Site 419
• Belgium
  • Aalst, Belgium, 9300
    • Site 328
  • Brussels, Belgium, B- 1200
    • Site 109
  • Charleroi, Belgium, 6000
    • Site 326
  • Hasselt, Belgium, 3500
    • Site 325
  • Leuven, Belgium, 3000
    • Site 108
  • Liège, Belgium, B-4000
    • Site 327
• Brazil
  • Porto Alegre, Brazil, 90035-001
    • Site 421
  • Rio De Janeiro, Brazil, 22250-905
    • Site 380
  • São Paulo, Brazil, 01321001
    • Site 376
  • São Paulo, Brazil, 01327-001
    • Site 389
  • São Paulo, Brazil, 01409-002
    • Site 413
  • São Paulo, Brazil, 01509-900
    • Site 374
  • São Paulo, Brazil, 01509010
    • Site 001
  • Bahia
    • Salvador, Bahia, Brazil, 41950-640
      • Site 384
  • Brasília - DF
    • Brasília, Brasília - DF, Brazil, 70297-400
      • Site 424
  • Ceara
    • Fortaleza, Ceara, Brazil, 60170-170
      • Site 382
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30210-040
      • Site 383
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59062-000
      • Site 390
  • SP
    • São Paulo, SP, Brazil, 01409-002
      • Site 413
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Site 117
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Site 273
• France
  • Lille, France, 59020
    • Site 306
  • Montpellier, France, 34298
    • Site 347
  • Nancy, France, 54100
    • Site 307
  • Nice, France, 06189
    • Site 310
  • Paris, France, 75015
    • Site 289
  • Plérin, France, 22190
    • Site 323
• Hungary
  • Budapest, Hungary, 1122
    • Site 322
  • Debrecen, Hungary, 4032
    • Site 290
  • Győr, Hungary, 9024
    • Site 348
• Israel
  • Haifa, Israel, 3436212
    • Site 309
  • Jerusalem, Israel, 911201
    • Site 080
  • Tel Aviv, Israel, 6423906
    • Site 203
• Italy
  • Catania, Italy, 95126
    • Site 321
  • Legnago, Italy, 37045
    • Site 320
  • Milano, Italy, 20141
    • Site 122
  • Pavia, Italy, 27100
    • Site 295
  • Roma, Italy, 161
    • Site 161
  • Rome, Italy, 00168
    • Site 124
  • Torino, Italy, 10128
    • Site 293
  • Treviso, Italy, 31100
    • Site 319
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • Site 397
  • Seoul, Korea, Republic of, 03080
    • Site 399
  • Seoul, Korea, Republic of, 03722
    • Site 398
  • Seoul, Korea, Republic of, 05505
    • Site 403
  • Seoul, Korea, Republic of, 06273
    • Site 400
  • Seoul, Korea, Republic of, 06351
    • Site 396
  • Seoul, Korea, Republic of, 08308
    • Site 402
  • Seoul, Korea, Republic of, 42601
    • Site 409
• Poland
  • Gdynia, Poland, 81-519
    • Site 341
  • Poznań, Poland, 61-886
    • Site 331
  • Siedlce, Poland, 08-110
    • Site 329
• Spain
  • Badalona, Spain, 08916
    • Site 349
  • San Sebastián, Spain, 20014
    • Site 311
  • Valencia, Spain, 46026
    • Site 330
• United Kingdom
  • Cheltenham, United Kingdom, GL53 7AN
    • Site 366
  • London, United Kingdom, NW1 2PG
    • Site 055
  • Manchester, United Kingdom, M20 4BX
    • Site 344
  • Northwood, United Kingdom, HA6 2RN
    • Site 345
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 1ES
      • Site 367
  • Somerset
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Site 351
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Site 318
    • Tucson, Arizona, United States, 85719
      • Site 277
  • California
    • Irvine, California, United States, 92618
      • Site 350
    • La Jolla, California, United States, 92093
      • Site 364
    • Palo Alto, California, United States, 94304
      • Site 150
    • San Francisco, California, United States, 94109
      • Site 278
    • San Francisco, California, United States, 94143
      • Site 014
    • Solvang, California, United States, 93463
      • Site 316
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Site 032
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Site 335
    • Weston, Florida, United States, 33331
      • Site 042
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Site 009
    • Atlanta, Georgia, United States, 30342
      • Site 272
    • Gainesville, Georgia, United States, 30548
      • Site 372
    • Savannah, Georgia, United States, 31405
      • Site 291
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Site 315
    • Hinsdale, Illinois, United States, 60521
      • Site 314
    • Urbana, Illinois, United States, 61801
      • Site 346
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Site 339
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Site 200
    • Overland Park, Kansas, United States, 66211
      • Site 334
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Site 279
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Site 128
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Site 288
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Site 292
  • New York
    • Flushing, New York, United States, 11355
      • Site 275
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Site 298
    • Cincinnati, Ohio, United States, 45459
      • Site 304
  • Oregon
    • Portland, Oregon, United States, 97210
      • Site 280
    • Portland, Oregon, United States, 97213
      • Site 317
    • Portland, Oregon, United States, 97239
      • Site 049
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • Site 337
    • Pittsburgh, Pennsylvania, United States, 15213
      • Site 127
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Site 276
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Site 368
    • Nashville, Tennessee, United States, 37203
      • Site 281
  • Texas
    • Austin, Texas, United States, 78731
      • Site 229
    • Bedford, Texas, United States, 76022
      • Site 312
    • Fort Worth, Texas, United States, 76104
      • Site 297
    • San Antonio, Texas, United States, 78240
      • Site 392
    • The Woodlands, Texas, United States, 77380
      • Site 301
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Site 300
    • Richmond, Virginia, United States, 23298
      • Site 365
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Site 121

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nab-paclitaxel 80 mg/m^2 with Relacorilant 150 mg; 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; Nab-paclitaxel is administered as intravenous (IV) infusion over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle.; Drug: Relacorilant 150 mg once daily (QD); Relacorilant is administered as capsules for oral dosing.
Active Comparator: 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.	Drug: Nab-paclitaxel 100 mg/m^2; Nab-paclitaxel is administered as IV infusion on Day 1, 8, and 15 of each 28-day cycle.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Collaborators: Gynecologic Oncology Group
• Investigators: Study Director: L. Dreiling, MD, Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 4, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Urogenital Neoplasms; Neoplasms by Site; Peritoneal Diseases; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Ovarian Neoplasms; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: CORT125134-556; GOG-3073 (Other Identifier: Gynecologic Oncology Group); ROSELLA Study 556 (Other Identifier: Corcept Therapeutics); ENGOT-OV72 (Other Identifier: European Network of Gyneaecological Oncological Trial Groups); APGOT-Ov10 (Other Identifier: Asia Pacific Gyneaecological Oncological Trial Groups); LACOG 0223 (Other Identifier: Latin America Cooperative Oncology Trials Group); ANZGOG2221/2023 (Other Identifier: Australia New Zealand Oncology Group)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No