Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer
Condition: Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: OSI-906; Everolimus
Intervention description: Dose Level 1: 50 mg Twice a Day, cycle-28 days Dose Level 2: 100 mg Twice a Day, cycle-28 days Dose Level 2a: 100 mg Twice a Day, cycle-28 days; Dose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days
Intervention MeSH terms: Everolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory metastatic colorectal cancer

Summary:

      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.
    

Eligibility criteria:

        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