OPSALIN: A phase II placebo-controlled randomized study of ombrabulin in patients with platinum-sensitive recurrent ovarian cancer treated with carboplatin (Cb) and paclitaxel (P).

Abstract

TPS5112 Background: Most women with ovarian cancer have disease recurrence after responding to their first treatment with platinum-based chemotherapy and are considered to have platinum-sensitive disease if the relapse-free period is more than 6 months. Although CbP is standard first-line chemotherapy for ovarian cancer, patients with platinum-sensitive recurrent disease are often retreated with CbP. Ombrabulin (AVE8062) is a vascular disrupting agent and analogue of combretastatin A4 that damages established tumor vasculature causing tumor necrosis and has synergistic antitumor activity with platinum agents in tumor models in vivo (Cancer Sci. 2003;94:200). A phase I study showed that treatment with vivo ombrabulin plus CbP is feasible in patients with advanced solid tumors (NCI-AACR-EORTC 2010;Abs 386). We initiated OPSALIN, a phase II randomized trial, to evaluate whether the addition of ombrabulin to CbP improves outcomes in patients with platinum-sensitive recurrent ovarian cancer (NCT01332656; EFC10260). Methods: Eligibility criteria include age of at least 18 years, ECOG PS 0–2, measurable carcinoma of the ovarian epithelium, fallopian tube, or primary peritoneum that is platinum sensitive, and completion of only one previous line of platinum-based chemotherapy. Exclusion criteria include uncontrolled brain metastases, peripheral neuropathy >grade 1, and a prior history of cardiovascular disease. Patients are being randomized (1:1) to receive either ombrabulin 35mg/m2 or placebo plus CbP every 3 weeks. Assigned treatment will continue until disease progression or death, unacceptable toxicity, or consent withdrawal. The primary endpoint is progression-free survival stratified by the time of first disease recurrence (6–12 months or >12 months). Secondary endpoints include safety, response rate, overall survival, pharmacokinetics, and analysis of predictive/prognostic biomarkers. Planned randomization is a total of 150 patients at approximately 45 sites globally. Sixty-five patients have been randomized as of January 2012.