Background: Angiogenesis is required for tumor growth and metastasis. Both VEGF and PDGFR are key regulators of tumor vasculature. In preclinical models, dual inhibition of VEGF and PDGFR signaling result in more effective tumor suppression and improved survival. We report the results of an expansion cohort of a phase I study targeting angiogenesis with sorafenib, bevacizumab and low-dose cyclophosphamide in children and young adults with solid tumors. Methods: The treatment doses and schedule of the combined therapy were derived from results of a previously reported dose-escalation phase I study (Navid F et al. Clin Cancer Res 2013). Four cohorts of 6 patients with refractory or recurrent solid tumors were enrolled and received bevacizumab (15mg/kg IV, day 1), sorafenib (90mg/m² po BID, days 1-21) and low-dose cyclophosphamide (50mg/m² po daily, days 1-21). Each course of therapy lasted 21 days. Serial bevacizumab pharmacokinetic (PK) studies were performed during course 1. Toxicity was assessed using CTCAE 3.0. Response was assessed using RECIST1.1. Results: Twenty-four patients (15 males; median age 14.5 yrs; range 1.1-22.4 yr) received a median of 6 courses (range 1-18) of therapy. Twelve patients had a bone or soft tissue sarcoma and 12 patients had a non-sarcoma solid tumor. The most common grade 3/4 non-hematologic toxicities were hypertension (4), hand/foot rash (3) and elevated lipase (3). The most common grade 3/4 hematologic toxicities were neutropenia (7) and lymphopenia (17). Three patients (2 synovial sarcoma, 1 rhabdoid tumor) achieved a partial response and 18 had disease stabilization. The progression-free survival at 3 and 6 months were 78.1% (95% CI 60.6-95.6%) and 54% (95% CI 30.2-78.2%). Bevacizumab PK studies were performed in 15 patients and the median (range) clearance, Cmax, Tmax and AUC were 4.4mL/day/kg (2.8-6.0), 331µg/mL (206-441), 1.9hrs (1.6-4.6) and 3345µg/mL*day (2566-5297) respectively. Conclusions: This treatment regimen is well tolerated and demonstrated promising activity in a variety of childhood solid tumors. Additional studies are warranted. Clinical trial information: NCT00665990