Importantly, in the first phase II trial, the treatment benefits of the combination therapy were achieved irrespective of homologous recombination repair (HRR) mutation status, which suggests a potential synergy between the two treatments. This may mean that patients without known DNA repair defects may still benefit from combination therapy.
PROpel (NCT03732820) is the title of the first Phase III trial to assess a PARP inhibitor in combination with abiraterone as first-line treatment in a genetically unselected mCRPC patient population. Enrollment began October 2018.
Study Design: PROpel is a double-blind, placebo-controlled, international, multicenter study of patients. Patients are randomized 1:1 to abiraterone (1000 mg daily plus prednisone/prednisolone 5 mg bid) plus either olaparib (tablets, 300 mg bid) or placebo.
The full protocol is below:
Imaging assessment will include CT and MRI scans of the Chest/Abdomen/Pelvis and a bone scan – performed at baseline, every 8 weeks until week 24, then every 12 weeks.
Cross-over is not allowed in this trial.
- Men aged 18+
- Histologically or cytologically confirmed prostate cancer
- Metastatic status defined by at least 1 metastatic site
- First-line treatment at the mCRPC stage
- ECOG 0-1
- Availability of FFPE tissue or new tumor biopsy tissue for HHR status evaluation
- Candidate for abiraterone therapy
- Patients must not have received prior chemotherapy, new hormonal agents or other systemic treatment at mCRPC stage – but they may have received prior docetaxel at metastatic hormone-sensitive prostate cancer stage [mHSPC]) per CHAARTED data.
- Patients will be excluded if: other malignancy is present, clinically significant cardiovascular risk, uncontrolled hypertension, planned cardiac intervention.
Outcomes: Primary endpoint is investigator-assessed radiographic progression-free survival (rPFS) per RECIST v1.1 [soft tissue] and Prostate Working Cancer Group 3 [PCWG3 criteria; bone].
Secondary objectives include:
- Time to first subsequent therapy or death
- Time to pain progression
- Time to second progression (PFS2)
- Overall survival
- Health-related quality of life (using BPI, FACT-P, and EQ-5D-5L)
Screening across ~200 sites in 20 countries is being conducted to identify a target sample of ~720 patients.
Enrollment began in October 2018
Preliminary Enrollment data: None provided
Presented by: Noel W Clarke, Professor of Urologic Oncology, Director of the Genitourinary Research Group, Manchester University, Consultant Urologist at Salford Royal Hospital and The Christie, Manchester
Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.
1. Clarke N et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):975-986. doi: 10.1016/S1470-2045(18)30365-6. Epub 2018 Jun 4.