The purpose of this study is to determine the maximum tolerated dose (MTD) of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer.

Inclusion Criteria:

• Metastatic cancer of the colon or rectum that has progressed on or for which the patient is intolerant to or not a candidate for: fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab.
• Testing for Kras mutation performed;Patients with mutated or wild type Kras are eligible.
• ECOG PS of 0-1
• Life expectancy of ≥ 3 months
• Adequate hematological function with ANC 1500, Platelets of 100,000, and hemoglobin of 9.0
• AST, ALT and Alk. Phos. ≤2.5 x ULN or ≤5 x ULN if known hepatic metastases and a total bilirubin ≤1.5 ULN
• Serum creatinine of ≤1.5 x ULN
• Fasting blood glucose <150 mg/dL
• Measurable disease according to RECIST 1.1
• Able to swallow whole pills
• INR ≤1.5 - Anticoagulation is allowed with LMW heparin
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN;If these thresholds are exceeded, the patient can be included after initiation of lipid lowering medication

Exclusion Criteria:

• Patients who have received any cancer therapies <4 weeks or 5 half lives (whichever is shorter) of initiating study therapy
• Treatment with any investigational drug ≤ 4 weeks, or 5 half-lives of the drug, whichever is shorter
• Patients who require coumadin for anticoagulation
• Patients who have had major surgery or significant traumatic injury ≤4 weeks of the of study treatment
• Minor surgery (with the exception of port placement) must be completed ≤ 7days prior to study therapy
• Previous treatment with an IGFR inhibitor or MTOR Inhibitor
• Chronic, systemic treatment with corticosteroids or another immunosuppressive agent
• Patients with QTc interval >450ms
• Patients who require drugs that can prolong QTc.
• Patients with congenital long QT syndrome, history of ventricular tachycardia, or ventricular fibrillation, or Torsades de Pointes with bradycardia.
• Immunization with attenuated live vaccines within 1 week of beginning study therapy or during study period;Close contact to anyone that has received live virus vaccine should be avoided
• Meningeal or brain metastasis
• Other malignancies < 3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, or carcinoma in situ of the cervix
• Patients with known HIV
• Patients with positive testing for hepatitis B or C
• Patients with risk factors for hepatitis must be tested for hepatitis viral loadHepatitis risk factors include the following:

Lived in Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece Any blood transfusions before 1990 Any IV drug use Any dialysis Household contact with a Hep B infected patient Mother had Hep B High-risk sexual activity Body piercing/tattoos

• History suggestive of hepatitis B
• Any severe or uncontrolled conditions that could affect their study participation such as:Severely impaired lung function;DCLO ≤ 50% of normal predicted value;O² Sat <88% at rest on room air
• Congestive Heart Failure of NYHA Class III or IV
• Unstable angina, symptomatic CHF, MI ≤ 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease
• CVA, TIA, angioplasty, or cardiac stenting <12 months
• Ventricular arrhythmia requiring medication
• Known history of diabetes and/or patients who require ongoing use of insulin or oral anti-hyperglycemic therapy
• Known liver disease
• Impairment of GI function or gastrointestinal disease that in may significantly alter the absorption of study drugs
• Concurrent treatment with drugs that are strong CYP3A4 inducers or moderate/strong CYP3A4 inhibitors
• Concurrent treatment with drugs that are strong CYP1A2 inhibitors or inducers Women who are pregnant or breastfeeding.
• Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements

18 months

All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.