Phase I/II trial of CCI 779 and bevacizumab in advanced renal cell carcinoma (RCC): Safety and activity in RTKI refractory RCC patients
5039 Background: Combined mTOR and VEGF blockade is a potentially promising and rational strategy for the treatment of advanced RCC. We previously reported the phase I safety and efficacy results of CCI 779 (C) +bevacizumab (B) n RTKI naïve stage IV RCC patients (pts) (J Clin Oncol. 2007;25[18S Suppl]:5034). We now report the interim results of the phase 2 study of C+B in RTKI refractory RCC patients. Methods: Design: Open label, phase I/II study of C+B in advanced RCC pts. Patients with measurable stage IV RCC with a component of clear/conventional cell type, performance status 0–2 and good organ function were eligible. Up to two prior treatment regimens were allowed (at least one prior RTKI). Phase II dose was C = 25 mg IV weekly and B = 10 mg/kg every 2 weeks repeated in 4 week cycles. The primary objective of the phase II portion was to assess the proportion of patients who were progression-free 6 months after study entry. Secondary objectives were assessment of response rates and toxicity. Accrual goal = 40 pts. Results: Thirty-five pts have been enrolled into the phase 2 portion to date with 4 pts ineligible. Twenty-five pts are evaluable for response assessment and 29 pts are evaluable for toxicity. Baseline characteristics (N: 35): M/F: 28/7; Number of met. sites: 1/2/3+: 15/9/11; prior nephrectomy: 31; Number of prior therapies: 1 = 29; 2 = 2. Most common (>5%) Gr 3–4 AEs (N = 29) included fatigue (6), hypercholesterolemia (2), hypertriglyceridemia (2), anorexia (2), rash (2), and anemia (2). Responses were: PR/SD/PD = 4 (16%)/18 (72%)/3 (12%). Median number of cycles administered was 4. Six month progression free rates will mature by may 2009. Conclusions: C+B combination at the recommended phase 2 doses is feasible and well tolerated. Clinical benefit rates (PR/SD) in RTKI refractory RCC patients (88%) are encouraging. Data on 6 month progression-free rates are expected to mature in 4/09. Updated data on safety, response rates, and 6-month progression free rates will be presented on all evaluable patients. Correlative studies on available plasma, serum and tumor samples for angiogenic and molecular biomarkers are underway. Supported by N01-CM62205, R21 CA 119545–02, and Commonwealth Foundation. [Table: see text]