VEGF-Trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC): Preliminary results of a randomized, multicenter phase II study

5508 Background: Vascular endothelial growth factor (VEGF) is over-expressed in EOC and associated with poor prognosis. VEGF Trap, a potent angiogenesis inhibitor fusion protein, is comprised of portions of human VEGF-receptor R1+R2 (Flt-1, KDR) extracellular domains and fused to the Fc portion of human IgG. VEGF Trap binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. Methods: This is a randomized, double blind, multicenter, 2-stage, phase II trial of VEGF Trap (2 or 4 mg/kg) administered intravenously every 2 weeks, in pts with recurrent EOC. Eligible criteria included 2 or 3 prior chemo regimens for advanced disease; platinum- resistance, topotecan- and/or liposomal doxorubicin-resistance; no prior VEGF inhibitor treatment; ECOG performance status 0–2; normal organ function; no proteinuria (<500 mg/24hrs or UPCR =1); controlled blood pressure. This Simon 2 stage design, requires 3 responders out of 42 evaluable, in each arm to continue accrual into stage 2. Results: Across 62 centers in Europe, Canada and US, rapid accrual led to 162 pts randomized from 5/06 to 12/06. Median age: 58, PS (0,1,2): 56,40,4%. Of 45 pts currently in the database, across the two arms, adverse events included (any grade): headache (38%), fatigue (36%), dysphonia (33%), nausea (29%), asthenia (24%), diarrhea (18%), hypertension (16%), proteinuria (7%), renal dysfunction (4%). Grade 3–4, included: hypertension (9%), proteinuria (4%), encephalopathy (2%) and renal failure (2%). Of the 162 pts who had at minimum one cycle, study drug-related SAE include (N): thrombocytopenia (1), anemia (1), headache (1) asthenia (2),dyspnea (1), hypertension (4), bowel perforation (2), encephalopathy (1), renal failure (2), proteinuria (1), phlebitis (1) and pulmonary embolism (1). 5 partial responses (11%) have been reported. Conclusions: VEGF Trap has activity in this heavily-pretreated EOC population. The first stage of accrual is complete and updated results will be presented. No significant financial relationships to disclose.