736P - Pantoprazole affecting docetaxel resistance pathways via autophagy (PANDORA): A phase II trial in men with metastatic castrate resistant prostate c...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Prostate Cancer
Presenter Aaron Hansen
Citation Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372
Authors A. Hansen1, I. Tannock1, A.J. Templeton1, A. Prawira1, J. Knox1, F. Vera-Badillo1, E. Chen1, M.B. Zavitz1, L. Wang2, A. Evans3, Q. Tan4, B. Wouters4, S. Sridhar1, A. Joshua1
  • 1Medical Oncology, Princess Margaret Cancer Centre, M5G 2M9 - Toronto/CA
  • 2Biomedical Statistics, University of Toronto, M5G 2M9 - Toronto/CA
  • 3Pathology, University Health Network, Toronto/CA
  • 4Campbell Family Institute For Cancer Research, University Health Network, Toronto/CA

Abstract

Background

Enhancing the effectiveness of docetaxel for men with mCRPC is an unmet clinical need. Preclinical studies in our laboratory demonstrated that high dose pantoprazole can prevent or delay resistance to docetaxel via the inhibition of autophagy in several solid tumor xenografts.

Methods

Men with chemotherapy-naïve mCRPC with a PSA >10ng/ml and adequate organ function were eligible for enrolment. The study regimen included intravenous pantoprazole (240mg) and docetaxel (75mg/m2) every 21 days, with continuous prednisone 5mg twice daily. The primary endpoint was a confirmed >50% decline of PSA. Progression free (PFS) and overall survival (OS) were assessed by the Kaplan-Meier method. This trial used a Simon's 2-stage design.

Results

Between November 2012 and March 2015, 21 men with a median age of 70 years (range 58-81 years) were treated (median 6 cycles, range 2 to 11). Participants (pts) had received prior systemic therapies (median 4, range 1 to 8) and 14 had received abiraterone and/or enzalutamide. The PSA response rate was 52% (11/21) which did not meet the prespecified criterion (≥13/21 responders) to proceed to stage 2 of the study. At interim analysis with a median follow-up of 12 months, 13 (62%) pts were deceased (10 CRPC, 2 unknown, 1 radiation complication). Of the pts with RECIST measurable disease, the radiographic partial response rate was 31% (4/13). The estimated median PFS was 5.3 months (95%CI: 2.6-12.9) and median OS was 15.7 months (95% CI: 9.3-19.6). There were no toxic deaths and most adverse events were attributed to docetaxel (hematological: 14% febrile neutropenia, 14% G4 neutropenia, 19% G3/4 anemia; non-hematological: 24% G3 fatigue and 5% G3 anorexia).

Conclusions

The combination of docetaxel and pantoprazole was tolerable, but the resultant clinical activity was not sufficient to meet the ambitious predefined target to warrant further testing. Planned correlative studies to evaluate tumor samples for autophagy are in progress, and are expected to provide insights into autophagy in the context of docetaxel resistance.

Clinical trial identification

NCT01748500

Legal entity responsible for the study

Princess Margaret Cancer Centre

Funding

Supported by a grant from the Canadian Institutes of Health Research.

Disclosure

All authors have declared no conflicts of interest.