CEBOC: Evaluation of the safety of Cediranib in the prevention of Bowel perforation in platinum-resistant Ovarian Cancer


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Ann White1,Andrew Clamp2,Robert Morgan2,Dilly Goonetilleke3,Angela Casbard4,Tracie-Ann Madden4,Jennifer Swettenham4,Alkesh Patel2,Charlotte Wilhelm-Benartzi4,Catherine Rogers2,Gordon Jayson2
1,2The Christie NHS Foundation Trust,3The University of Manchester,4Cardiff University

Abstract

Background

The principal cause of death from ovarian cancer is malignant bowel obstruction (MBO). This trial aims to identify a safe treatment option for ovarian cancer patients at risk of developing MBO. CEBOC will test cediranib (VEGF receptor tyrosine kinase inhibitor) in combination with paclitaxel, in women at risk of developing bowel obstruction from ovarian cancer. CEBOC will closely monitor safety, in particular bowel perforation/fistulas.

Method

A single arm, two stage, single-centre study of cediranib 20 mg od with paclitaxel 70 mg/m2/week in patients with recurrent platinum-resistant ovarian cancer, with clinical or radiological features indicating an increased risk of MBO. Participants will receive paclitaxel for 6 cycles (21-day cycle) with cediranib introduced if bowel symptoms have stabilised after 6 cycles, participants can continue single agent cediranib 20 mg od until progressive disease (PD). Participants may then continue cediranib plus the PARP inhibitor, olaparib (300mg/bi-daily), until further PD. The primary outcome is the number of participants free of grade 3-5 gastrointestinal perforation/fistula, after starting cediranib.

Stage 1: 9 out of 10 evaluable participants must be free of perforation/fistula events six weeks after starting cediranib in order for the trial to continue. Stage 2: 14 more participants will be recruited. Recruitment will stop if ≥3 participants experience a perforation/fistula. In total 24 evaluable patients (receive cediranib for >5 days) with ovarian cancer at high risk of MBO will be recruited.

The trial opened in Oct 2017 (EudraCT: 2016-004618-93; Sponsor: University of Manchester; Funder: AstraZeneca).

Results

We have recruited thirteen patients and we expect recruitment to be complete by Autumn 2020.

Conclusion

CEBOC will evaluate the safety and activity of a cediranib-paclitaxel combination in women with ovarian cancer at high risk of MBO. The regimen will be considered acceptably safe if ≥22 out of 24 participants are free of perforations/fistulas.