Phase I Study of Cetuximab With RO4929097 in Metastatic Colorectal Cancer

PRIMARY OBJECTIVES: I. Determination of the maximum tolerated dose (MTD) of the combination of cetuximab and RO4929097. SECONDARY OBJECTIVES: I. Safety and tolerability of the combination of cetuximab and RO4929097. II. Exploratory analyses of anti-tumor effect with the combination. III. Laboratory correlatives exploring response rate with notch receptors and ligand expression, correlation of response and toxicity profiles to expression of EGFR pathway components, and evaluation of serum and tissue markers of gamma-secretase inhibitor activity. IV. Pharmacokinetic studies. OUTLINE: This is a dose-escalation study of gamma-secretase/Notch signalling pathway inhibitor RO4929097. Phase I dose escalation: In this part of the study, the investigators are trying to find out what is the highest tolerated dose of RO4929097 that can be safely combined with cetuximab. The investigators will be testing two different cetuximab doses. One is the standard dose (Arm A) and one is a little less than the standard dose (Arm B). Everyone will get treated with cetuximab and R04929097 in this part of the study. Phase I dose expansion: In this part of the study, the investigators will take the highest tolerated dose found in the phase I part of the study and test a small number of people with colorectal cancer to see if there is any activity with the combination of drugs. Everyone will get treated with cetuximab and RO4929097 in this part of the study. This part of the study will be restricted to patients whose tumors do not have a mutation in the K-ras gene. RO4929097 is an investigational anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in colorectal cancer. Cetuximab is FDA approved for metastatic colorectal cancer. After completion of study treatment, patients are followed up every 3 months.