956P - A phase Ib and randomised phase II trial of pazopanib with or without fosbretabulin in advanced recurrent ovarian cancer

Abstract

Background: Prospective trials have validated angiogenesis as a treatment target in ovarian cancer although improvements in PFS have been modest. One potential strategy to improve efficacy is to combine anti-vascular agents. Fosbretabulin (F) is an intravenous vascular disrupting agent and pazopanib (P) is an oral VEGFR tyrosine kinase inhibitor. Methods: A multi-centre Phase 1b(P1b)/randomised phase 2 (RP2) trial that recruited women with recurrent epithelial ovarian cancer and a platinum-free interval of 3-12 months. Any Bevacizumab had been received ≥6 months prior to recruitment. Phase 1b dose levels ranged from F = 54mg/m2 d1,8,15q28d + P = 600mg/day (F54+P600) up to F = 60mg/m2 d1,8,15q28d + P = 800mg/day. In RP2 participants received either RP2D or P = 800mg/day (P800). Primary outcome in P1b was safety plus RP2D and in RP2 was RECIST PFS. Results: 12 and 21 patients were recruited to P1b & RP2 respectively. The RP2D was F54+P600. In the RP2 median PFS was 7.6 months (95%CI 4.1-not estimated) in F54+P600 group vs. 3.7 months (95%CI 1.0-8.1) in P800 group (HR 0.30, 95%CI 0.08-1.03, P = 0.06). Four patients who received F+P (2 in P1b and 2 in RP2) developed acute hypertension plus reversible secondary cardiac toxicity. The occurrence of cardiac toxicity resulted in premature discontinuation of the trial. Data on circulating biomarkers of angiogenesis collected in in P1b & RP2 will also be presented. Conclusions: F54+P600 appeared effective but was associated with reversible secondary cardiac toxicity that with better hypertension control might have been avoided. Clinical trial identification: EudraCT: 2013-005471-40. Legal entity responsible for the study: The Christie NHS Foundation Trust. Funding: Novartis & Mateon Therapeutics. Disclosure: G.J.S. Rustin: Advisory board: Mateon, Roche, AstraZeneca in past 3 years, only Roche in past year. All other authors have declared no conflicts of interest.