everolimus and osi-906 for patients with refractory metastatic colorectal cancer

Conditions: 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

Keywords: refractory metastatic colorectal cancer