Despite many advances in cancer therapy, metastatic disease continues to be incurable in the majority of cancer patients. There ia an need for more efficient and less toxic treatments is this setting. Oncolytic virotherapy represents a novel promising direction in the treatment of cancer. Based on preclinical and clinical data, combination with standard chemotherapy has the potential to further increase the antitumor activity of oncolytic virotherapy in a synergistic manner. We present the design of a phase I clinical trial combining intratumoral injections of the oncolytic adenovirus ONYX-015 with systemic chemotherapy in patients with advanced sarcomas.