Phase II trial of olaparib in patients with advanced castration resistant prostate cancer.
Disease site: Prostate cancer, urological cancers
Treatment modality: Systemic therapy
Status: In follow up
TOPARP is an open label, two part adaptive design phase II trial to evaluate the anti-tumour activity of the PARP inhibitor olaparib in metastatic castration resistant prostate cancer. The trial will also identify molecular signatures of tumour cells in responding and non-responding patients, and clinically qualify putative predictive biomarkers of PARP inhibitor sensitivity.
Part A of TOPARP (TOPARP-A) closed to recruitment in October 2014 after recruiting 50 patients, who received 400 mg olaparib twice daily. The results were presented at the American Association of Cancer Research (AACR) conference in April 2015 and also published in the New England Journal of Medicine in October 2015.
Part B of TOPARP (TOPARP-B) closed to recruitment in July 2018 after recruiting a total of 98 patients. Potential participants had their tumour tissue analysed and only those with biomarkers predictive of olaparib response were eligible to enter TOPARP-B. Half of patients received 300 mg twice daily, and half received 400 mg of olaparib twice daily.
In both parts of TOPARP, patients receive olaparib until disease progression, after which they are followed up for an end of treatment safety assessment and every 3 months for life.
Chief Investigator: Professor Johann de Bono, The Institute of Cancer Research
ICR-CTSU Scientific Lead: Prof Emma Hall
Trial management contact: [email protected]
Sponsor: The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust
Funding: Cancer Research UK (CRUK/11/029) and AstraZeneca
Further information, including recruitment progress, is available from the UK Clinical Trials Gateway portfolio.
A plain English summary of TOPARP is available from Cancer Research UK.
Publications and presentations
1. A’Hern R, DeBono J, Sandhu S, Kalaitzaki E, Usdin M, HALL E (2011). Phase II investigation of a PARP inhibitor (olaparib) in castration resistant prostate cancer (CRPC) which incorporates the possibility that treatment effect may be restricted to biomarker defined subgroups. Trials 12 (Suppl 1): #A88
(Oral presentation at Clinical Trials Methodology conference 2011, Bristol, UK)
2. A’Hern R, DeBono J, Sandhu S, Kalaitzaki E, Usdin M, HALL E (2012). A two-stage phase II design incorporating the possibility that the treatment effect may be restricted to a biomarker defined subgroup: investigation of a PARP inhibitor (olaparib) in castration resistant prostate cancer (CRPC). Clin Trials 9(4):552 #P116
(Poster presentation at the Society for Clinical Trials 2012 33rd Annual Meeting, Miami, Florida)
3. J. Mateo, E. Hall, S. Sandhu, A.G. Omlin1, S. Miranda, S. Carreira, J. Goodall, A. Gillman, H. Mossop, C. Ralph, Z. Zafeiriou, R. Perez Lopez, N. Tunariu, R. Ferraldeschi, D. Nava, Rodrigues, L.P. Kunju, D. Robinson, G. Attard, A. Chinnaiyan, J.S. De Bono (2014). Antitumour activity of the PARP inhibitor olaparib in unselected sporadic castration-resistant prostate cancer (CRPC) in the TOPARP trial. Ann Oncol 25(Suppl 4):#LBA20
(Oral presentation at European Society for Medical Oncology, Madrid, Spain 2014)
4. Joaquin Mateo, Shahneen Sandhu, Susana Miranda, Suzanne Carreira, Suneil Jain, Christy Ralph, Andrew Protheroe, Syed Hussain, Robert Jones, Tony Elliot, Ursula McGovern, Alexa Gillman, Claire Paulding, Helen Mossop, Nuria Porta, Diletta Bianchini, Zafeiris Zafeiriou, Gunther Boysen, Daniel Nava Rodrigues, Penelope Flohr, George Seed, Jane Goodall, Ines Figueiredo, Raquel Perez-Lopez, Nina Tunariu, Aurelius Omlin, Roberta Ferraldeschi, Lakshmi P. Kunju, Rosalind Eeles, Gerhardt Attard, Dan Robinson, Arul Chinnaiyan, Emma Hall, Johann S. de Bono. DNA repair defects and antitumor activity with PARP inhibition: TOPARP, a phase II trial of olaparib in metastatic castration resistant prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT322. doi:10.1158/1538-7445.AM2015-CT322
(Oral Presentation at American Association for Cancer Research, Philadelphia, America 2015)
6. Raquel Perez-Lopez, Matthew D. Blackledge, Joaquin Mateo, David J. Collins, Veronica A. Morgan, Alison MacDonald, Diletta Bianchini, Zafeiris Zafeiriou, Pasquale Rescigno, Michael Kolinsky, Daniel Nava Rodrigues, Helen Mossop, Nuria Porta, Emma Hall, Martin O. Leach, Johann S. de Bono, Dow-Mu Koh, and Nina Tunariu. Diffusion Weighted Imaging (DWI) as a Treatment Response Biomarker in Prostate Cancer Bone Metastases
(Multimedia poster presentation at ISMRM, Singapore 2016)
7. Joaquin Mateo, Suzanne Carreira, Helen Mossop, Pasquale Rescigno, Michael Kolinsky, Elena Castro, Ada Balasopoulou, Jo Hunt, Desamparados Roda, Claudia Bertan, Jane Goodall, Susana Miranda, Penny Flohr, Nuria Porta, Zsofia Kote-Jarai, David Olmos, Christopher Lord, Emma Hall, Ross Eeles, Johann S. de Bono. DNA Repair Gene Aberrations in Germline DNA in Metastatic Castration-Resistant Prostate Cancer Patients. #4340
(Oral presentation at American Association for Cancer Research, New Orleans 2016)
8. Raquel Perez-Lopez, Matthew D. Blackledge, Helen Mossop, Joaquin Mateo, David Collins, Veronica A. Morgan, Alison McDonald, Shahneen Sandhu, Aurelius Omlin, Diletta Bianchini, Zafeiris Zafeiriou, Pasquale Rescigno, Michael Kolinsky, Daniel Nava Rodrigues, Penny Flohr, Berni Ebbs, Gemma Fowler, Nuria Porta, Emma Hall, Martin Leach, Johann S. de Bono, Dow-Mu Koh, Nina Tunariu. Diffusion-weighted Imaging of Bone Metastases as Treatment Response Biomarker in Prostate Cancer. Clin Research; #3973.
(Poster presentation at American Association for Cancer Research, New Orleans, US, 2016)
9. Joaquin Mateo, Helen Mossop, Jane Goodall, David Lorente, Nuria Porta, Suzanne Carreira, Susana Miranda, Zafeiris Zafeiriou, Christy Ralph, Suneil Jain, Robert J. Jones, Syed A. Hussain, Tony Elliott, Andrew Protheroe, Berni Ebbs, Lorna Leonard, Diletta Bianchini, Penelope Flohr, Emma Hall, Johann S. De Bono (2016). Changes in circulating cell-free plasma DNA (cfDNA) and circulating tumor cells (CTC) during treatment associate with clinical outcome from olaparib in castration-resistant prostate cancer (CRPC); exploratory analyses from the TOPARP-A trial.
(Poster presentation, GUASCO, Orlando, US 2017)
10. Joaquin Mateo, Suzanne Carreira, George Seed, Rob Chandler, David Dolling, Ines Figueiredo, Susana Miranda, Daniel Nava Rodrigues, Claudia Bertan, Diletta Bianchini, Christy Ralph, Robert Jones, Ursula McGovern, Mohini Varughese, Omi Parikh, Suneil Jain, Tony Elliot, Nuria Porta, Emma Hall, Johann S. de Bono (2018). Genomic profiling of primary prostate tumors from patients who develop metastatic castration-resistant prostate cancer (mCRPC)
(Poster presentation, ASCO, Chicago, US 2018)
1. J. Mateo, S. Carreira, S. Sandhu, S. Miranda, H. Mossop, R. Perez-Lopez, D. Nava Rodrigues, D. Robinson, A. Omlin, N. Tunariu, G. Boysen, N. Porta, P. Flohr, A. Gillman, I. Figueiredo, C. Paulding, G. Seed, S. Jain, C. Ralph, A. Protheroe, S. Hussain, R. Jones, T. Elliott, U. McGovern, D. Bianchini, J. Goodall, Z. Zafeiriou, C T. Williamson, R. Ferraldeschi, R. Riisnaes, B. Ebbs, G. Fowler, D. Roda, W. Yuan, Y. Wu, X. Cao, R. Brough, H. Pemberton, R. A’Hern, A. Swain, L. P. Kunju, R. Eeles, G. Attard, C. J. Lord, M. Rubin, K. Knudsen, F. Feng, A. M. Chinnaiyan, E. Hall, J.S. de Bono. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer; N Engl J Med 2015; 373:16971708. October 29, 2015
2. R. Perez-¬Lopez, M.D. Blackledge, H. Mossop, J. Mateo, D.J. Collins, V.A. Morgan, A. McDonald, S. Sandhu, A. Omlin, D. Bianchini, Z. Zafeiriou, P. Rescigno, M. Kolinsky, D. Nava Rodrigues, P. Flohr, B. Ebbs, G. Fowler, N. Porta, E. Hall, M.O. Leach, J.S. de Bono, D-M. Koh, N. Tunariu (2016). Diffusion-weighted imaging as a treatment response biomarker evaluating bone metastases in prostate cancer: A Pilot Study. Radiology 2016.
3. Jane Goodall*, Joaquin Mateo*, Wei Yuan, Helen Mossop, Nuria Porta, Susana Miranda, Raquel Perez-Lopez, David Dolling, Dan Robinson, Shahneen Sandhu, Gemma Fowler, Berni Ebbs, Penny Flohr, George Seed, Daniel Nava-Rodrigues, Gunther Boysen, Claudia Bertan, Mark Atkin, Mateus Crespo, Ines Figueiredo, Ruth Riisnaes, Semini Sumanasuriya, Pasquale Rescigno, Zafeiris Zafeiriou, Nina Tunariu, Diletta Bianchini, Alexa Gillman, Chris Lord, Emma Hall, Arul M. Chinnaiyan, Suzanne Carreira#, Johann S. de Bono#, on behalf of the TOPARP-A investigators. Circulating Free DNA Testing to Guide Prostate Cancer Treatment with PARP Inhibition. Cancer Discov August 31 2017 7 (9) 1006-1017; DOI:10.1158/2159-8290.CD-17-0261
This research was funded by the Stand Up to Cancer campaign for Cancer Research UK.