Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102

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