COPELIA: A Randomised Phase II Trial of Cediranib in Combination with Paclitaxel or Olaparib Versus Weekly Paclitaxel Chemotherapy as Second-Line Therapy for Advanced/Metastatic Endometrial Cancer


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Jennifer Swettenham1,Gordon Jayson2,Robert Morgan2,Dilly Goonetilleke3,Richard Edmondson3,Ann White4,Angela Casbard1,Tracie-Ann Madden1,Nisa Khan2,Charlotte Wilhelm-Benartzi1,Catherine Rogers2,Rebecca Kristeleit5,Andrew Clamp2
1Cardiff University,2The Christie NHS Foundation Trust,3University of Manchester,4,5University College London

Abstract

Background

The incidence of endometrial cancer and its associated mortality are increasing. Approximately 20% of patients develop recurrent disease after surgery and 25-30% present with advanced disease. Prognosis is poor for these patients and there is urgent need for an effective therapy. The COPELIA trial aims to find an effective treatment for patients with advanced/metastatic endometrial cancer.

Data suggest synergistic potential from combining VEGF inhibitors with chemotherapy (Aparna 2007; Pignata 2015; Pujade-Lauraine 2012; 2014). Endometrial cancer cells are sensitive to PARP inhibitors (Miyasaka 2014), which also combine effectively with VEGF inhibitors (Liu 2013, 2014, 2015). COPELIA tests the benefit of cediranib-paclitaxel and cediranib-olaparib combinations compared with paclitaxel alone.

Method

COPELIA is a randomised, controlled, 3-arm, open-label, multi-stage, phase II trial. Patients (n=129) with metastatic endometrial carcinoma/carcinosarcoma will be randomised 1:1:1 to: paclitaxel (80 mg/m2 IV on 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, whilst cediranib and olaparib may continue until disease progression.

The primary outcome is the proportion of participants free from progressive disease three months after starting trial treatment. Secondary outcomes include tolerability and quality of life.

With paclitaxel only, ~50% of patients are expected to be free from progressive disease at three months (Fleming 2015; Oza 2015). The trial is powered for an improvement in either experimental arm to 70%. An interim analysis after 20 participants in each arm have completed three months will allow one experimental arm to be dropped, or the trial stopped, if there is lack of benefit.

The trial will open at 15 UK sites from Oct/2017 (EudraCT: 2016-004617-28; Sponsor: University of Manchester; Funder: AstraZeneca).

Results

Recruitment aims to complete by Apr/2020.

Conclusion

COPELIA will define the efficacy of the paclitaxel-cediranib and olaparib-cediranib combinations, in metastatic endometrial cancer.