Phase II trial FOLFOX combined with Bevacizumab, Cetuximab and Imatinib in patients with advanced untreated colorectal cancer

Primary objectives: High complete response rate 25 defined as complete disappearance of all signs and symptoms of the disease as well as no imaging CT and serologic CEA evidence of disease.
Primary endpoints: We aim at a high rate of sustained CR 25 lasting a minimum of 12 months . If we could show a 25 CR rate in the setting, no matter how selected the patients are as long as they have non resectable metastases at presentation , anybody should agree that this approach should be further pursued. There are 2 components to this endpoint - the high rate of CR - and the very long minimal duration of the achieved CR at least 12 mo . We fully realize that this is very ambitious goal. The CR rate to CT alone in these setting is below 5 and the R0 resectability rate in advanced CRC is in the range of 10 . The median duration of NED state following R-0 resection, i.e. the DFS, varies according to the starting conditions, but the most reliable figure for patients with initially non respectable liver mets is around 6 months S. Alberts, Mayo, 2006, n 40 patients . This in general should be regarded too short a figure to make a liver resection acceptable. The cost of medical treatment plan under investigation is prohibitive. If all 3 biologics plus CT are regularly taken, the cost of the drugs hospital pharmacy cost is around 9000 per month. And if we count an average of 15.000 for the liver resection, the entire treatment plan for 6 months of medical treatment plus the cost of surgery is in the range of 70.000 per patient. This figure is so high that anything below the threshold we identified 25 CR rate woul be socially unacceptable . Thus the new endpoint 25 NED state lasting at least 12 months is compromise among. A very ambitious, still plausible cut off CR rate. A very rilevant finding that would be worthwhile pursuing only if the chances of fooling ourselves in this pilot experience are low and they should be very low, given the stringent eligibility criteria. Through a lot of interdisciplinary discussion, instead of referring to CR, that is usually a condition achieved through medical treatment, we are using the term NED, because it entails both the CR obtained medically and those obtained surgically, it is a widely recognized term. The duration of it can be implemented as further sine qua non of the novel endpoint. In addition the Bryant Day statistical design of this entails no more than 40 severe toxicity of the chemo-biologic part of the treatment.