Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer

OUTLINE: This is a multi-center study. PHASE I: * UGT1A1 \*28 7/7 genotype IS NOT present * Cetuximab 250 mg/m2 IV days 1, 8, and 15 * Irinotecan 125 mg/m2 IV days 1 and 8 * RAD001 PO QD (dose determined at the time of registration; subjects will remain at this dose level until treatment discontinuation) PHASE II: * Randomization based on UGT1A1 \*28 7/7 Genotype or Prior Irinotecan Exposure ARM A: * Cetuximab 250 mg/m2 IV days 1, 8, and 15 * Irinotecan 125 mg/m2 IV days 1 and 8 AT TIME OF PROGRESSIVE DISEASE, ARM A TREATMENT WILL CROSSOVER: * Cetuximab 250 mg/m2 IV days 1, 8, and 15 * Irinotecan 125 mg/m2 IV days 1 and 8 * RAD001 PO QD (maximum tolerated dose) ARM B: * Cetuximab 250 mg/m2 IV days 1, 8, and 15 * Irinotecan 125 mg/m2 IV days 1 and 8 * RAD001 PO QD (maximum tolerated dose) AT TIME OF PROGRESSIVE DISEASE, ARM B TREATMENT WILL BE DISCONTINUED ECOG performance status 0-2 Life Expectancy: Not specified Hematopoietic: * Absolute neutrophil count (ANC) ≥ 1,500 mm3 * Platelets ≥ 100,000 mm3 * Hemoglobin (Hgb) ≥ 9 g/dL * White blood cell count (WBC) ≥ 2,000 mm3 * INR \< 1.5 x upper limit of normal (ULN) if not on anticoagulation (if on anticoagulation must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin) * PTT \< 1.5 x ULN Hepatic: * Bilirubin ≤ 1.5 x ULN * Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN * Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN * Albumin ≥ 3.0 g/dL Renal: * Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula Cardiovascular: * No uncontrolled cardiac arrhythmia requiring medication, transient ischemic attack (TIA), or cerebrovascular accident (CVA) within 6 months prior to being registered for protocol therapy * No uncontrolled congestive heart failure, myocardial infarction, or unstable angina within 6 months prior to being registered for protocol therapy Pulmonary: * No severely impaired lung function as demonstrated by pulse O2 saturation ≤ 90% at rest on room air, or pulmonary function test FEV1 ≤ 2L * No history of prior chronic lung infection such as tuberculosis, atypical tuberculosis, or histoplasmosis as evidenced by a chest CT or x-ray within 21 days prior to being registered for protocol therapy