Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): A randomised, multicentre, double-blind, placebo-controlled phase 3 trial

Bradley J. Monk, Andrés Poveda, Ignace Vergote, Francesco Raspagliesi, Keiichi Fujiwara, Duk Soo Bae, Ana Oaknin, Isabelle Ray-Coquard, Diane M. Provencher, Beth Y. Karlan, Catherine Lhommé, Gary Richardson, Dolores Gallardo Rincón, Robert L. Coleman, Thomas J. Herzog, Christian Marth, Arija Brize, Michel Fabbro, Andrés Redondo, Aristotelis BamiasMarjan Tassoudji, Lynn Navale, Douglas J. Warner, Amit M. Oza

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Abstract

Background: Angiogenesis is a valid target in the treatment of epithelial ovarian cancer. Trebananib inhibits the binding of angiopoietins 1 and 2 to the Tie2 receptor, and thereby inhibits angiogenesis. We aimed to assess whether the addition of trebananib to single-agent weekly paclitaxel in patients with recurrent epithelial ovarian cancer improved progression-free survival. Methods: For this randomised, double-blind phase 3 study undertaken between Nov 10, 2010, and Nov 19, 2012, we enrolled women with recurrent epithelial ovarian cancer from 32 countries. Patient eligibility criteria included having been treated with three or fewer previous regimens, and a platinum-free interval of less than 12 months. We enrolled patients with a computerised interactive voice response system, and patients were randomly assigned using a permuted block method (block size of four) in a 1:1 ratio to receive weekly intravenous paclitaxel (80 mg/m2) plus either weekly masked intravenous placebo or trebananib (15 mg/kg). Patients were stratified on the basis of platinum-free interval (≥0 and ≤6 months vs >6 and ≤12 months), presence or absence of measurable disease, and region (North America, western Europe and Australia, or rest of world). The sponsor, investigators, site staff, and patients were masked to the treatment assignment. The primary endpoint was progression-free survival assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT01204749, and is no longer accruing patients. Findings: 919 patients were enrolled, of whom 461 were randomly assigned to the trebananib group and 458 to the placebo group. Median progression-free survival was significantly longer in the trebananib group than in the placebo group (7·2 months [5·8-7·4] vs 5·4 months [95% CI 4·3-5·5], respectively, hazard ratio 0·66, 95% CI 0·57-0·77, p

Original languageEnglish
Pages (from-to)799-808
Number of pages10
JournalThe Lancet Oncology
Volume15
Issue number8
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Oncology

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Monk, B. J., Poveda, A., Vergote, I., Raspagliesi, F., Fujiwara, K., Bae, D. S., Oaknin, A., Ray-Coquard, I., Provencher, D. M., Karlan, B. Y., Lhommé, C., Richardson, G., Rincón, D. G., Coleman, R. L., Herzog, T. J., Marth, C., Brize, A., Fabbro, M., Redondo, A., ... Oza, A. M. (2014). Anti-angiopoietin therapy with trebananib for recurrent ovarian cancer (TRINOVA-1): A randomised, multicentre, double-blind, placebo-controlled phase 3 trial. The Lancet Oncology, 15(8), 799-808. https://doi.org/10.1016/S1470-2045(14)70244-X