OCTOPUS: A randomised, multi-centre phase II umbrella trial of weekly paclitaxel+/- novel agents in platinum-resistant ovarian cancer—Vistusertib (AZD2014).

Abstract

TPS5609 Background: There is an urgent need to improve outcomes for patients with platinum-resistant and refractory ovarian cancer (PROC). OCTOPUS is an umbrella phase II framework for testing whether the addition of novel targeted agents to weekly paclitaxel (wPxl) improves efficacy in PROC. The first agent to be evaluated is the dual mTORC1/mTORC2 inhibitor, vistusertib (AZD2014), as preclinical studies support targeting the PI3kinase/Akt/mTOR pathway in PROC and the combination of vistusertib and wPxl has shown promising preliminary activity in high grade serous ovarian cancer (HGS) patients in a phase I trial (Banerji et al poster discussion ESMO 2016). This is the first randomised trial of wPxl and a dual mTORC1/2 inhibitor in ovarian cancer. Methods: OCTOPUS is an investigator-initiated, randomised, double-blind, placebo-controlled, multicentre, phase II trial. 140 patients with PROC (histologically confirmed HGS) are randomised 1:1 to receive wPxl (80mg/m2 D1, D8, D15 of 28 day cycle) plus oral vistusertib (50mg BD) or placebo (D1-3, D8-10, D15-17). The primary endpoint is progression-free survival (PFS) based on combined RECIST v1.1/GCIG CA125 criteria. The study is designed to detect a 50% improvement in median PFS from 3.7 months on placebo to 5.55 months on the experimental arm with 90% power, at the 20% 1-sided level of statistical significance (or equivalently with 80% power at the 10% level of statistical significance) using a 3-outcome design. Secondary endpoints include response (based on RECIST 1.1 and GCIG CA125 criteria), overall survival, toxicity and quality of life. Patients whom received prior wPxl for PROC are not eligible. A mandatory pre-treatment biopsy (if technically feasible), archival tissue, and serial blood samples will be collected for translational research studies. 49 patients have been recruited. The study is part of the NIHR CRN Cancer/Astrazeneca Alliance, sponsored by NHS Greater Glasgow and Clyde/University of Glasgow and endorsed by Cancer Research UK (CRUKE/14/052). Clinical trial information: ISRCTN16426935.