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

NCT ID: NCT01154335

Last Updated: 2022-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-05-31

Brief 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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level 1

combination of OSI-906 and everolimus

OSI-906: 50 mg Twice a Day, cycle-28 days

Everolimus: 5mg Daily, cycle-28 days

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

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

Everolimus

Intervention Type: DRUG

Dose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days

Dose Level 2

combination of OSI-906 and everolimus

OSI-906: 100 mg Twice a Day, cycle-28 days

Everolimus: 10mg Daily, cycle-28 days

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

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

Everolimus

Intervention Type: DRUG

Dose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days

Dose Level 2a

combination of OSI-906 and everolimus

OSI-906: 100 mg Twice a Day, cycle-28 days

Everolimus: 5mg Daily, cycle-28 days

Group Type: EXPERIMENTAL

OSI-906

Intervention Type: DRUG

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

Everolimus

Intervention Type: DRUG

Dose Level 1: 5mg Daily, cycle-28 days Dose Level 2: 10mg Daily, cycle-28 days Dose Level 2a: 5mg Daily, cycle-28 days

Interventions

OSI-906

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

Intervention Type: DRUG

Everolimus

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 Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

OSI Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johanna Bendell, MD

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Florida Cancer Specialists

Fort Myers, Florida, United States

Tennessee Oncology

Nashville, Tennessee, United States

Countries

United States

References

Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C, Infante JR, Barton J, Burris HA. A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. Invest New Drugs. 2015 Feb;33(1):187-93. doi: 10.1007/s10637-014-0177-3. Epub 2014 Oct 22.

Reference Type: DERIVED

PMID: 25335932 (View on PubMed)

Other Identifiers

SCRI GI 124

Identifier Type: -

Identifier Source: org_study_id