COPELIA: A Randomised Phase II Trial of Cediranib in Combination with Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy for Advanced Endometrial Cancer


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Joanna Canham1,Gordon Jayson2,Robert Morgan2,Clare Freestone3,Angela Casbard4,Terri Kitson4,Alkesh Patel2,Chelsey Wheeler2,Rebecca Kristeleit5,Marcia Hall6,Louise Hanna7,Axel Walther8,Susana Banerjee9,Rene Roux10,Azmat Sadoyze11,Yvette Drew12,Andrew Clamp2
1WCTU, Cardiff University,2The Christie NHS Foundation Trust,3Centre For Trials Research,4Centre for Trials Research,5University College London,6Mount Vernon Hospital,7Velindre NHS Trust,8University Hospitals Bristol NHS Foundation Trust,9The Royal Marsden NHS Foundation Trust,10Oxford University Hospitals NHS Foundation Trust,11Greater Glasgow Health Board,12The Newcastle upon Tyne Hospitals NHS Foundation Trust

Abstract

Background

The incidence of endometrial cancer (EC) is rising rapidly. Prognosis is poor for patients who present with advanced disease or develop recurrence after primary treatment. There is an urgent need for more effective therapies. COPELIA evaluates 2 novel treatment strategies based on genomic and preclinical data supporting both angiogenesis and DNA repair as potential targets in EC. VEGF inhibitors have promising activity in recurrent EC (Bender 2015) and have synergistic effects with weekly chemotherapy (Pignata 2015; Pujade-Lauraine 2014) and Poly-ADP ribose polymerase inhibitors (Liu 2014) in other cancers. COPELIA tests the benefit of cediranib-paclitaxel and cediranib-olaparib combinations compared with paclitaxel alone.

Method

COPELIA is a randomised, 3-arm, open-label, multi-arm-multistage phase II trial. Patients (n=129) with metastatic EC/carcinosarcoma will be randomised 1:1:1 to paclitaxel (80 mg/m2 IV days 1, 8, 15 of 28-day cycle); paclitaxel plus cediranib (20mg/day PO); or cediranib plus olaparib (300mg/bi-daily PO). Paclitaxel will not be given beyond six cycles, cediranib and olaparib may continue until disease progression.

 

Primary outcome is the proportion of participants free from progressive disease at three months (PFS3). Secondary outcomes include tolerability and quality of life. Translational research will evaluate angiogenesis-related cytokines, circulating tumour cells and measures of homologous recombination DNA repair competency.

With weekly paclitaxel , PFS3 is expected to be~50% (Fleming 2015; Oza 2015). The trial is powered for an improvement in either experimental arm to 70%. An interim analysis with the potential early termination of either test arm for lack of benefit after 20 participants in each arm have RECIST data available at 3 months. (EudraCT :2016-004617-28; Sponsor: University of Manchester; Funder: AstraZeneca).

Results

The trial is open at 9 of 15 planned sites. 13 patients have been randomised. Projected recruitment completion - Oct 2020.

Conclusion

COPELIA will estimate the efficacy of the paclitaxel-cediranib and olaparib-cediranib combinations in metastatic endometrial cancer