Approximately 18% of patients (pts) with high-grade epithelial ovarian cancer (OC) harbour a deleterious germline BRCA1 or BRCA2 (BRCA1/2) mutation, and ≈7% harbour a somatic BRCA1/2 mutation (Pennington et al. Clin Cancer Res. 2014;20:764-75). The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib is approved in the United States for the treatment of pts with deleterious BRCA mutation (germline and/or somatic) associated advanced OC who have been treated with ≥2 chemotherapies. Data comparing PARP inhibitors to standard of care (SOC) treatment for relapsed OC are limited. Randomised studies are needed to assess the benefit-risk profile of PARP inhibitors vs SOC as treatment for BRCA1/2-mutated, relapsed, high-grade OC.
ARIEL4 (EudraCT 2016-000816-14; NCT02855944) is evaluating rucaparib vs SOC chemotherapy as treatment for pts (n≈345) with relapsed, high-grade OC (regardless of histology) and a deleterious germline or somatic BRCA1/2 mutation who received ≥2 prior chemotherapy regimens. Pts stratified by progression-free interval after their most recent platinum regimen will be randomised 2:1 to receive rucaparib (600 mg BID) (n≈230) or chemotherapy (n≈115). Pts with platinum-resistant (progressive disease [PD] ≥1 to < 6 mo after last platinum) or partially platinum-sensitive disease (PD ≥ 6 to < 12 mo after last platinum) will receive rucaparib or weekly paclitaxel; pts with platinum-sensitive disease (PD ≥ 12 mo after last platinum) will receive rucaparib or platinum-based therapy (single-agent or doublet, per investigator discretion). Pts receiving chemotherapy have the option to cross over to rucaparib upon radiographic disease progression. The primary endpoint is investigator-assessed progression-free survival (RECIST version 1.1). Secondary endpoints include overall survival, objective response rate, RECIST/CA-125 response, duration of response, and patient-reported outcomes. Safety will be summarised descriptively using standard adverse event reporting.
Clinical trial identification
EudraCT 2016-000816-14; NCT02855944
Legal entity responsible for the study
Clovis Oncology, Inc.
Clovis Oncology, Inc.
R.S. Kristeleit: Consulting or advisory role: Clovis Oncology, Roche/Genentech, Sotio, Lytix Biopharma, Medivation Travel, Accommodations, Expenses: Clovis Oncology, Basilea Honoraria: Clovis Oncology, Roche/Genentech, AstraZeneca. D. Lorusso: Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Roche, PharmaMar Travel, Accommodations, Expenses: Roche, PharmaMar. A. Oaknin: Consulting or Advisory Role: PharmaMar, Clovis Oncology, Roche, AstraZeneca. C. Tankersley, L. Maloney, S. Goble, A. Dowson, H. Giordano: Employment: Clovis Oncology Stock and Other Ownership Interests: Clovis Oncology. C. Unger: Employment: Clovis Oncology Stock and Other Ownership Interests: Clovis Oncology, Sillajen. A.M. Oza: Consulting or Advisory Role: Amgen, Verastem, Clovis Oncology, Immunovaccine Travel, Accommodations, Expenses: AstraZeneca Honoraria: WebRx. All other authors have declared no conflicts of interest.