Background Cediranib is a highly potent vascular endothelial growth factor (VEGF) signaling inhibitor of all three VEGF receptors. This phase I, single-center, dose-finding study was designed primarily to investigate the safety and pharmacokinetics (PK) of cediranib with various anticancer regimens in patients with advanced solid tumors. Experimental design Oral cediranib 20, 30, and/or 45 mg/day was given in combination with standard mFOLFOX6; docetaxel; irinotecan; irinotecan and cetuximab; or pemetrexed. The novel study design allowed simultaneous evaluation of the safety and PK of these regimens with cediranib in one study. Secondary assessments included a preliminary evaluation of efficacy. Results Fifty-nine patients received cediranib and were evaluable for safety. The most common adverse events across the study were fatigue and diarrhea (both n = 52). The most common CTC grade ≥ 3 adverse events were neutropenia (n = 19) and fatigue (n = 16). Cediranib did not appear to have a major effect on the PK profile of any chemotherapy agent tested. A preliminary assessment of efficacy showed that objective responses were achieved in some patients (n = 6) who had previously progressed on similar regimens without cediranib. Conclusion In this group of heavily pretreated patients, the study design permitted simultaneous assessment of multiple treatment arms. Treatment with cediranib and the various anticancer regimens was generally well tolerated, with no apparent PK interaction and preliminary evidence of antitumor activity.