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

Peritoneal Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05257408
• Other study ID #: CORT125134-556
• Secondary ID: ROSELLA Study 55
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 29, 2022
• Est. completion date: June 2025

Study information

• Verified date: April 2024
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fallopian Tube Neoplasms
• Neoplasms
• Ovarian Neoplasm
• Ovarian Neoplasms
• Peritoneal Neoplasms

Intervention

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.
• Relacorilant 150 mg once daily (QD)
Relacorilant is administered as capsules for oral dosing.
• Nab-paclitaxel 100 mg/m^2
Nab-paclitaxel is administered as IV infusion on Day 1, 8, and 15 of each 28-day cycle.

Locations

Country	Name	City	State
Argentina	Site 393	Caba	Buenos Aires
Argentina	Site 381	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Site 395	Ciudad de Cordoba	Cordoba
Argentina	Site 401	Ciudad de Cordoba	Cordoba
Argentina	Site 415	Ciudad de Cordoba	Cordoba
Argentina	Site 404	Ciudad de Mendoza	Mendoza
Argentina	Site 391	Rosario	Santa Fe
Argentina	Site 412	Rosario	Santa Fe
Australia	Site 417	Benowa	Queensland
Australia	Site 414	Melbourne	Victoria
Australia	Site 419	Melbourne	Victoria
Australia	Site 426	St. Leonards	New South Wales
Belgium	Site 328	Aalst
Belgium	Site 109	Brussels
Belgium	Site 326	Charleroi
Belgium	Site 325	Hasselt
Belgium	Site 108	Leuven
Belgium	Site 327	Liège
Brazil	Site 383	Belo Horizonte	Minas Gerais
Brazil	Site 424	Brasília	Brasília - DF
Brazil	Site 382	Fortaleza	Ceara
Brazil	Site 390	Natal	Rio Grande Do Norte
Brazil	Site 421	Porto Alegre
Brazil	Site 380	Rio De Janeiro
Brazil	Site 384	Salvador	Bahia
Brazil	Site 001	São Paulo
Brazil	Site 374	São Paulo
Brazil	Site 376	São Paulo
Brazil	Site 389	São Paulo
Brazil	Site 413	São Paulo
Brazil	Site 413	São Paulo	SP
Canada	Site 273	Montréal	Quebec
Canada	Site 117	Toronto	Ontario
France	Site 306	Lille
France	Site 347	Montpellier
France	Site 307	Nancy
France	Site 310	Nice
France	Site 289	Paris
France	Site 323	Plérin
Hungary	Site 322	Budapest
Hungary	Site 290	Debrecen
Hungary	Site 348	Gyor
Israel	Site 309	Haifa
Israel	Site 080	Jerusalem
Israel	Site 203	Tel Aviv
Italy	Site 321	Catania
Italy	Site 320	Legnago
Italy	Site 122	Milano
Italy	Site 295	Pavia
Italy	Site 161	Roma
Italy	Site 124	Rome
Italy	Site 293	Torino
Italy	Site 319	Treviso
Korea, Republic of	Site 397	Gyeonggi-do
Korea, Republic of	Site 396	Seoul
Korea, Republic of	Site 398	Seoul
Korea, Republic of	Site 399	Seoul
Korea, Republic of	Site 400	Seoul
Korea, Republic of	Site 402	Seoul
Korea, Republic of	Site 403	Seoul
Korea, Republic of	Site 409	Seoul
Poland	Site 341	Gdynia
Poland	Site 331	Poznan
Poland	Site 329	Siedlce
Spain	Site 349	Badalona
Spain	Site 311	San Sebastián
Spain	Site 330	Valencia
United Kingdom	Site 367	Brighton	East Sussex
United Kingdom	Site 366	Cheltenham
United Kingdom	Site 055	London
United Kingdom	Site 344	Manchester
United Kingdom	Site 345	Northwood
United Kingdom	Site 351	Taunton	Somerset
United States	Site 292	Albuquerque	New Mexico
United States	Site 009	Atlanta	Georgia
United States	Site 272	Atlanta	Georgia
United States	Site 032	Aurora	Colorado
United States	Site 229	Austin	Texas
United States	Site 312	Bedford	Texas
United States	Site 337	Bethlehem	Pennsylvania
United States	Site 128	Boston	Massachusetts
United States	Site 298	Cincinnati	Ohio
United States	Site 304	Cincinnati	Ohio
United States	Site 315	Evanston	Illinois
United States	Site 275	Flushing	New York
United States	Site 297	Fort Worth	Texas
United States	Site 372	Gainesville	Georgia
United States	Site 368	Germantown	Tennessee
United States	Site 314	Hinsdale	Illinois
United States	Site 339	Indianapolis	Indiana
United States	Site 350	Irvine	California
United States	Site 364	La Jolla	California
United States	Site 279	Louisville	Kentucky
United States	Site 335	Miami Beach	Florida
United States	Site 121	Milwaukee	Wisconsin
United States	Site 281	Nashville	Tennessee
United States	Site 288	New Brunswick	New Jersey
United States	Site 300	Norfolk	Virginia
United States	Site 200	Overland Park	Kansas
United States	Site 334	Overland Park	Kansas
United States	Site 150	Palo Alto	California
United States	Site 318	Phoenix	Arizona
United States	Site 127	Pittsburgh	Pennsylvania
United States	Site 049	Portland	Oregon
United States	Site 280	Portland	Oregon
United States	Site 317	Portland	Oregon
United States	Site 276	Rapid City	South Dakota
United States	Site 365	Richmond	Virginia
United States	Site 392	San Antonio	Texas
United States	Site 014	San Francisco	California
United States	Site 278	San Francisco	California
United States	Site 291	Savannah	Georgia
United States	Site 316	Solvang	California
United States	Site 301	The Woodlands	Texas
United States	Site 277	Tucson	Arizona
United States	Site 346	Urbana	Illinois
United States	Site 042	Weston	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Corcept Therapeutics	Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  France,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	Time from randomization to death by any cause	Up to 24 months from enrollment of the last patient
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Clinical benefit rate as assessed by BICR	Proportion of patients who attain CR, PR, or stable disease (SD) per RECIST v1.1.	24 weeks
Secondary	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
Secondary	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