Clinical trial NCT05257408: Relacorilant in Combination With Nab-Paclitaxel in Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Ovarian Neoplasm
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group
First posted: 2022-02-25
Enrollment: 381
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival as Assessed by BICR
timeFrame: Up to 24 months from enrollment of the last patient
measure: Overall survival
timeFrame: Up to 24 months from enrollment of the last patient
Secondary outcomes:
measure: PFS as Assessed by the Investigator
timeFrame: Up to 24 months from enrollment of the last patient
measure: Objective Response as Assessed by BICR
timeFrame: Up to 24 months from enrollment of the last patient
measure: Best Overall Response as Assessed by BICR
timeFrame: Up to 24 months from enrollment of the last patient
measure: Duration of Response as Assessed by BICR
timeFrame: Up to 24 months from enrollment of the last patient
measure: Clinical benefit rate as assessed by BICR
timeFrame: 24 weeks
measure: Cancer Antigen (CA)-125 Response
timeFrame: Up to 24 months from enrollment of the last patient
measure: Combined Response According to RECIST v1.1 and GCIG Criteria
timeFrame: Up to 24 months from enrollment of the last patient
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Site 318
state: Arizona
city: Tucson
country: United States
facility: Site 277
state: Arizona
city: Irvine
country: United States
facility: Site 350
state: California
city: La Jolla
country: United States
facility: Site 364
state: California
city: Palo Alto
country: United States
facility: Site 150
state: California
city: San Francisco
country: United States
facility: Site 278
state: California
city: San Francisco
country: United States
facility: Site 014
state: California
city: Solvang
country: United States
facility: Site 316
state: California
city: Aurora
country: United States
facility: Site 032
state: Colorado
city: Miami Beach
country: United States
facility: Site 335
state: Florida
city: Weston
country: United States
facility: Site 042
state: Florida
city: Atlanta
country: United States
facility: Site 009
state: Georgia
city: Atlanta
country: United States
facility: Site 272
state: Georgia
city: Gainesville
country: United States
facility: Site 372
state: Georgia
city: Savannah
country: United States
facility: Site 291
state: Georgia
city: Evanston
country: United States
facility: Site 315
state: Illinois
city: Hinsdale
country: United States
facility: Site 314
state: Illinois
city: Urbana
country: United States
facility: Site 346
state: Illinois
city: Indianapolis
country: United States
facility: Site 339
state: Indiana
city: Overland Park
country: United States
facility: Site 200
state: Kansas
city: Overland Park
country: United States
facility: Site 334
state: Kansas
city: Louisville
country: United States
facility: Site 279
state: Kentucky
city: Boston
country: United States
facility: Site 128
state: Massachusetts
city: New Brunswick
country: United States
facility: Site 288
state: New Jersey
city: Albuquerque
country: United States
facility: Site 292
state: New Mexico
city: Flushing
country: United States
facility: Site 275
state: New York
city: Cincinnati
country: United States
facility: Site 298
state: Ohio
city: Cincinnati
country: United States
facility: Site 304
state: Ohio
city: Portland
country: United States
facility: Site 280
state: Oregon
city: Portland
country: United States
facility: Site 317
state: Oregon
city: Portland
country: United States
facility: Site 049
state: Oregon
city: Bethlehem
country: United States
facility: Site 337
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Site 127
state: Pennsylvania
city: Rapid City
country: United States
facility: Site 276
state: South Dakota
city: Germantown
country: United States
facility: Site 368
state: Tennessee
city: Nashville
country: United States
facility: Site 281
state: Tennessee
city: Austin
country: United States
facility: Site 229
state: Texas
city: Bedford
country: United States
facility: Site 312
state: Texas
city: Fort Worth
country: United States
facility: Site 297
state: Texas
city: San Antonio
country: United States
facility: Site 392
state: Texas
city: The Woodlands
country: United States
facility: Site 301
state: Texas
city: Norfolk
country: United States
facility: Site 300
state: Virginia
city: Richmond
country: United States
facility: Site 365
state: Virginia
city: Milwaukee
country: United States
facility: Site 121
state: Wisconsin
city: Caba
country: Argentina
facility: Site 393
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Site 381
state: Buenos Aires
city: Ciudad de Cordoba
country: Argentina
facility: Site 415
state: Cordoba
city: Ciudad de Cordoba
country: Argentina
facility: Site 401
state: Cordoba
city: Ciudad de Cordoba
country: Argentina
facility: Site 395
state: Cordoba
city: Ciudad de Mendoza
country: Argentina
facility: Site 404
state: Mendoza
city: Rosario
country: Argentina
facility: Site 391
state: Santa Fe
city: Rosario
country: Argentina
facility: Site 412
state: Santa Fe
city: St. Leonards
country: Australia
facility: Site 426
state: New South Wales
city: Benowa
country: Australia
facility: Site 417
state: Queensland
city: Melbourne
country: Australia
facility: Site 414
state: Victoria
city: Melbourne
country: Australia
facility: Site 419
state: Victoria
city: Aalst
country: Belgium
facility: Site 328
city: Brussels
country: Belgium
facility: Site 109
city: Charleroi
country: Belgium
facility: Site 326
city: Hasselt
country: Belgium
facility: Site 325
city: Leuven
country: Belgium
facility: Site 108
city: Liège
country: Belgium
facility: Site 327
city: Salvador
country: Brazil
facility: Site 384
state: Bahia
city: Brasília
country: Brazil
facility: Site 424
state: Brasília - DF
city: Fortaleza
country: Brazil
facility: Site 382
state: Ceara
city: Belo Horizonte
country: Brazil
facility: Site 383
state: Minas Gerais
city: Natal
country: Brazil
facility: Site 390
state: Rio Grande Do Norte
city: São Paulo
country: Brazil
facility: Site 413
state: SP
city: Porto Alegre
country: Brazil
facility: Site 421
city: Rio De Janeiro
country: Brazil
facility: Site 380
city: São Paulo
country: Brazil
facility: Site 376
city: São Paulo
country: Brazil
facility: Site 389
city: São Paulo
country: Brazil
facility: Site 413
city: São Paulo
country: Brazil
facility: Site 374
city: São Paulo
country: Brazil
facility: Site 001
city: Toronto
country: Canada
facility: Site 117
state: Ontario
city: Montréal
country: Canada
facility: Site 273
state: Quebec
city: Lille
country: France
facility: Site 306
city: Montpellier
country: France
facility: Site 347
city: Nancy
country: France
facility: Site 307
city: Nice
country: France
facility: Site 310
city: Paris
country: France
facility: Site 289
city: Plérin
country: France
facility: Site 323
city: Budapest
country: Hungary
facility: Site 322
city: Debrecen
country: Hungary
facility: Site 290
city: Győr
country: Hungary
facility: Site 348
city: Haifa
country: Israel
facility: Site 309
city: Jerusalem
country: Israel
facility: Site 080
city: Tel Aviv
country: Israel
facility: Site 203
city: Catania
country: Italy
facility: Site 321
city: Legnago
country: Italy
facility: Site 320
city: Milano
country: Italy
facility: Site 122
city: Pavia
country: Italy
facility: Site 295
city: Roma
country: Italy
facility: Site 161
city: Rome
country: Italy
facility: Site 124
city: Torino
country: Italy
facility: Site 293
city: Treviso
country: Italy
facility: Site 319
city: Gyeonggi-do
country: Korea, Republic of
facility: Site 397
city: Seoul
country: Korea, Republic of
facility: Site 399
city: Seoul
country: Korea, Republic of
facility: Site 398
city: Seoul
country: Korea, Republic of
facility: Site 403
city: Seoul
country: Korea, Republic of
facility: Site 400
city: Seoul
country: Korea, Republic of
facility: Site 396
city: Seoul
country: Korea, Republic of
facility: Site 402
city: Seoul
country: Korea, Republic of
facility: Site 409
city: Gdynia
country: Poland
facility: Site 341
city: Poznań
country: Poland
facility: Site 331
city: Siedlce
country: Poland
facility: Site 329
city: Badalona
country: Spain
facility: Site 349
city: San Sebastián
country: Spain
facility: Site 311
city: Valencia
country: Spain
facility: Site 330
city: Brighton
country: United Kingdom
facility: Site 367
state: East Sussex
city: Taunton
country: United Kingdom
facility: Site 351
state: Somerset
city: Cheltenham
country: United Kingdom
facility: Site 366
city: London
country: United Kingdom
facility: Site 055
city: Manchester
country: United Kingdom
facility: Site 344
city: Northwood
country: United Kingdom
facility: Site 345
Study officials:
affiliation: Corcept Therapeutics
name: Sachin Pai, MD
role: STUDY_DIRECTOR
References: