Phase I clinical trial of lenalidomide in combination with bevacizumab in patients with advanced cancer

Purpose Lenalidomide and bevacizumab have antitumor activity in various tumor types. We conducted a phase I study of this combination in patients with advanced cancer. Patients and methods A “3 + 3” study design was used. Lenalidomide 10 or 20 mg (orally, days 1-21) and bevacizumab 5, 7.5, or 10 mg/kg, (intravenously, every 2 weeks) were given at four escalating dose levels, followed by an expansion phase at the highest maximum tolerated dose (MTD) (1 cycle = 4 weeks). Dose-limiting toxicity (DLT), MTD, adverse events, and clinical outcomes were assessed. Results Thirty-one patients were enrolled (median age, 60 years; men, 52%). The most common tumor types were colorectal carcinoma (n = 11) and melanoma (n = 5). Overall, 105 cycles (median, 2) were administered. No DLTs were observed. The maximum tested dose (level 4) was used in the expansion phase. The most common toxicities were fatigue (n = 7, 23%) and skin rash (n = 4, 13%). One patient developed a transient ischemic attack (3.2%); prophylactic anticoagulation became mandatory in the subsequent 17 treated patients. Of 31 patients, 27 were evaluable for response. Stable disease (SD) was noted in 10 (37%) patients, including five patients with SD for ≥6 months (tumor types: clear cell sarcoma, germ cell tumor, colorectal carcinoma, and melanoma). The median progression-free survival and overall survival were 2.8 and 5.5 months, respectively. Conclusions The combination of lenalidomide with bevacizumab in patients with advanced solid tumors was safe. Prolonged stable disease was noted in selected tumor types, warranting further clinical evaluation.