Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer

• Status: Completed
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SCRI Development Innovations, LLC
• Collaborators: Novartis Pharmaceuticals; OSI Pharmaceuticals
• Treatments: Everolimus; Sirolimus

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