Table 2. Ongoing and completed trials of PARP inhibitors in prostate cancer.
| Name of trial | Identifier | Drug | Phase/design | Eligibility | Primary endpoint | Status |
|---|---|---|---|---|---|---|
| A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer (TOPARP) | NCT01682772 | Olaparib | Phase 2 single-group assignment (n=89) | mCRPC with progression one or two prior chemotherapies | PSA response rate/ objective response rate | Completed |
| Studying the Effects of Olaparib (± Degarelix) Given to Men With Intermediate/High Risk Prostate Cancer Before Radical Prostatectomy (CaNCaP03) | NCT02324998 | Olaparib +/− degarelix | Phase 1 RCT (n=20) | Intermediate/high risk patients with planned RP | PARP inhibition by change in IHC levels of biomarkers such as PAR, gamma H2AX, pH2A(s129), Rad51 foci, FANCD2 foci, ATM/ATR/CHK1/2 | Recruiting |
| Olaparib With or Without Cediranib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer | NCT02893917 | Olaparib +/− cediranib | Phase 2 RCT (n=84) | Two prior therapies | Radiographic progression free survival | Recruiting |
| A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON2) | NCT02952534 | Rucaparib | Phase 2 single group assignment (n=160) | HR deficiency, after taxane and 1–2 next gen AR inhibitors | PSA response rate/objective response rate | Recruiting |
| A Study of Rucaparib Verses Physician’s Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON3) | NCT02975934 | Rucaparib vs. abiraterone, enzalutamide, or docetaxel | Phase 3 RCT (n=400) | BRCA1/2/ATM mutation, progression after 1 next gen AR | Radiographic progression free survival | Recruiting |
| An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies (Galahad) | NCT02854436 | Niraparib | Phase 2 single group assignment (n=160) | DDR anomaly, and progression on AR therapy and taxane | Objective response rate (RECIST criteria) | Recruiting |
| Enzalutamide and Niraparib in the Treatment of Metastatic Castrate-Resistant Prostate Cancer | NCT02500901 | Niraparib + enzalutamide | Phase 1 single group assignment (n=2) | CRPC and progression with 1 prior chemo | MTD | Terminated |
| Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis | NCT03047135 | Olaparib | Phase 2 single group assignment (n=50) | Post-RP BCR, +/– prior salvage, non-metastatic disease | PSA response rate | Recruiting |
| Phase II Study to Evaluate Olaparib With Abiraterone in Treating Metastatic Castration Resistant Prostate Cancer | NCT01972217 | Olaparib + abiraterone vs. abiraterone | Phase 2 double-blind RCT (n=159) | Progression on docetaxel for mCRPC | Radiographic progression free survival | Active, not recruiting |
| BRCAAway: A Randomized Phase II Trial of Abiraterone, Olaparib, or Abiraterone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects | NCT03012321 | Olaparib vs. olaparib + abiraterone vs. abiraterone | Phase 2 crossover assignment (n=70) | mCRPC with HR deficiency | Objective progression free survival | Recruiting |
| A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib vs. Enzalutamide or Abiraterone Acetate in Men With mCRPC with HR Gene Mutations (PROfound) | NCT02987543 | Olaparib vs. olaparib + enzalutamide/abiraterone | Phase 3 RCT (n=340) | HR mutation after progression on ADT | Radiographic progression free survival | Recruiting |
| Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) | NCT02861573 | Olaparib + pembrolizumab, pembrolizumab +docetaxel + prednisone, pembrolizumab + enzalutamide | Phase 1 parallel assignment (n=180) | Cohort A-after docetaxel, cohort B-after abiraterone/enzalutamide, cohort c-after abiraterone | PSA response rate | Recruiting |
| Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad) | NCT03076203 | Niraparib + radium-223 | Phase 1 single group assignment (n=6) | Progression on ADT | MTD | Recruiting |
| A Safety and Pharmacokinetics Study of Niraparib Plus Androgen Receptor-Targeted Therapy (Apalutamide or Abiraterone Acetate Plus Prednisone) in Men With Metastatic Castration-Resistant Prostate Cancer | NCT02924766 | Niraparib + apalutamide or abiraterone | Phase 1 single group assignment (n=60) | Progression on AR targeted therapy and docetaxel | MTD | Recruiting |
| A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer | NCT01576172 | Veliparib + abiraterone vs. abiraterone | Phase 2 RCT (n=148) | Patients with and without ETS fusion with progression on ADT | PSA response rate | Recruiting |
| A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies | NCT01085422 | Veliparib + temozolomide | Phase 1 single Group assignment (n=35) | mCRPC with docetaxel progression | PSA response rate | Completed |
| Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial) | NCT03040791 | Nivolumab | Phase 2 single group assignment (n=29) | mCRPC after taxane-based chemotherapy progression with DNA repair defects | PSA response rate | Recruiting |
| Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer | NCT02861573 | Pembrolizumab + olaparib vs. pembrolizumab + docetaxel + prednisone vs. pembrolizumab + enzalutamide | Phase 2 parallel assignment (n=180) | mCRPC and either progressed on docetaxel or enzalutamide | PSA response rate | Recruiting |
| Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients with mCRPC with Homologous Recombination DNA Repair Deficiency | NCT03442556 | Induction with docetaxel and carboplatin + rucaparib camsylate maintenance | Phase 2 single group assignment (n=20) | mCRPC and progression on docetaxel, sipuleucel-T, abiraterone, and or cabazitaxel (no prior platinum/PARP) | Radiographic progression free survival | Not yet recruiting |
PARP, poly-ADP-ribose polymerase; mCRPC, metastatic castration-resistant prostate cancer; PSA, prostate specific antigen; RCT, randomized controlled trial; RP, radical prostatectomy; PAR, poly(ADP-ribose); ATM, ataxia-telangiectasia-mutated; ATR, ataxia-telangietctasia and Rad3-related; CHK, checkpoint kinase; HR, homologous recombination; AR, androgen receptor; DDR, DNA damage repair; RECIST, response evaluation criteria in solid tumors; MTD, maximum tolerated dose; BCR, biochemical recurrence; ADT, androgen deprivation therapy; ETS, E26 transformation-specific.