TOPARP: A Phase II Trial of Olaparib in Patients With Advanced Castration Resistant Prostate Cancer
Summary
This is an open-label, single arm, two part adaptive design phase II trial of Olaparib in patients with advanced castration resistant prostate cancer. The trial aims to evaluate the the anti-tumour activity of Olaparib in metastatic castration resistant prostate cancer, identify molecular signatures of tumour cells in responding and non-responding patients, and to identify predictive biomarkers of Olaparib response.
Timeline
- Start
- 2012-07
- Primary completion
- 2019-03
- Completion
- 2020-02
Outcome
Mixed primary results
paper If at least 19 (43%) of 44 evaluable patients in a dose cohort responded, then the dose cohort would be considered successful. PMID 31806540 ↗
paper Confirmed composite response was achieved in 25 (54·3%; 95% CI 39·0-69·1) of 46 evaluable patients in the 400 mg cohort PMID 31806540 ↗
paper and 18 (39·1%; 25·1-54·6) of 46 evaluable patients in the 300 mg cohort. PMID 31806540 ↗
Publications
- Carmichael J, Figueiredo I, Gurel B, Beije N, Yuan W, Rekowski J, Seed G, Carreira S, Bertan C, Fenor de La Maza MLD, Chandran K, Neeb A, Welti J, Gallagher L, Bogdan D, Crespo M, Riisnaes R, Ferreira A, Miranda S, Lu J, Shen MM, Hall E, Porta N, Westaby D, Guo C, Grochot R, Lord CJ, Mateo J, Sharp A, de Bono J. RNASEH2B loss and PARP inhibition in advanced prostate cancer. J Clin Invest. 2024 Jun 4;134(21):e178278. doi: 10.1172/JCI178278.
- Mateo J, Porta N, Bianchini D, McGovern U, Elliott T, Jones R, Syndikus I, Ralph C, Jain S, Varughese M, Parikh O, Crabb S, Robinson A, McLaren D, Birtle A, Tanguay J, Miranda S, Figueiredo I, Seed G, Bertan C, Flohr P, Ebbs B, Rescigno P, Fowler G, Ferreira A, Riisnaes R, Pereira R, Curcean A, Chandler R, Clarke M, Gurel B, Crespo M, Nava Rodrigues D, Sandhu S, Espinasse A, Chatfield P, Tunariu N, Yuan W, Hall E, Carreira S, de Bono JS. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jan;21(1):162-174. doi: 10.1016/S1470-2045(19)30684-9. Epub 2019 Dec 2.
- Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. doi: 10.1056/NEJMoa1506859.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Olaparib | Small molecule | 300 mg | Oral |
| Subject | Olaparib | Small molecule | 400 mg | Oral |