Grant: Fellowship - PA: CIHR/Rx&D - CAMO Research Program

Colorectal cancer is the second leading cause of cancer death in Canada. Over the last 10 years combination chemotherapy regimens containing irinotecan and oxaliplatin have emerged as new standards for initial treatment of metastatic colorectal cancer (mCRC). In addition, agents blocking tumor blood vessel growth (vascular endothelial growth factor (VEGF)) have demonstrated additional benefits when added to chemotherapy. Different combinations and sequences of administering these agents have been shown to affect cancer progression, patient survival and toxicity. To minimize toxicity and visits for intravenous treatments an effective, minimally toxic, oral maintenance therapy regimen after response to the initial chemotherapy treatment would be useful. One potential maintenance strategy is the use of low-dose metronomic (LDM) chemotherapy, which consists of administering very low doses of conventional anti-cancer drugs, such as cyclophosphamide, to kill cancer cells and block the growth of new blood vessels to the cancer. Adding an agent that blocks the VEGF pathway, such as cediranib, may be even more effective. The purpose of this clinical trial is to determine whether LDM cyclophosphamide and cediranib will delay time to progression of the cancer compared to cyclophosphamide and placebo. Sixty-four patients with mCRC who have responded to and completed at least 6 months of first-line chemotherapy and bevacizumab will be randomly assigned to either cyclophosphamide and cediranib or cyclophosphamide and placebo. The patients will be evaluated in clinic every 4 weeks and medical imaging will be assessed every 12 weeks. If the result of this study is positive, there would be evidence that the combination of LDM cyclophosphamide and cediranib is effective, and further testing in larger clinical trials would be warranted.