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

Inclusion Criteria:

* Histological or cytological proof of colon or rectal adenocarcinoma
* Measurable site of disease according to RECIST that has not been previously irradiated
* Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab
* Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 \*28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)
* A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer
* Prior radiation therapy allowed to \< 25% of the bone marrow
* Age ≥ 18 years at the time of consent
* Written informed consent and HIPAA authorization for release of personal health information
* Females of childbearing potential and males must be willing to use an effective method of contraception
* Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy

Exclusion Criteria:

* No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy
* No prior treatment with cetuximab
* No prior treatment with an mTOR inhibitor
* No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients
* No treatment with any investigational agent within 28 days prior to being registered for protocol therapy
* No symptomatic brain metastasis
* No uncontrolled diabetes as defined by a fasting serum glucose \>1.5 x ULN
* No chronic treatment with systemic steroids or another immuno-suppressive agent
* No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy
* No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
* No active bleeding or a pathological condition that is associated with a high risk of bleeding
* No uncontrolled systemic disease including active infections or uncontrolled hypertension
* No known history of HIV seropositivity
* No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
* No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy
* No planned immunization with attenuated live viruses during the study period
* Females must not be breastfeeding