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

SCRI Development Innovations

Status and phase: Completed; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Everolimus; Drug: OSI-906

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01154335

SCRI GI 124

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Dose Level 1

Experimental group

Description:

combination of OSI-906 and everolimus OSI-906: 50 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days

Treatment:

Drug: OSI-906

Drug: Everolimus

Dose Level 2

Experimental group

Description:

combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 10mg Daily, cycle-28 days

Treatment:

Drug: OSI-906

Drug: Everolimus

Dose Level 2a

Experimental group

Description:

combination of OSI-906 and everolimus OSI-906: 100 mg Twice a Day, cycle-28 days Everolimus: 5mg Daily, cycle-28 days

Treatment:

Drug: OSI-906

Drug: Everolimus