Clinical trial NCT01154335: Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer
Official title: A Phase I Study of Everolimus (mTOR Inhibitor) and OSI-906 (Dual IGFR and IR Tyrosine Kinase Inhibitor) for the Treatment of Patients With Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Colorectal Cancer
Keywords: refractory metastatic colorectal cancer
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: OSI Pharmaceuticals
First posted: 2010-06-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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.
timeFrame: 18 Months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 18 Months
measure: Overall Survival (OS)
timeFrame: 18 months
measure: Response Rate
timeFrame: 18 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Johanna Bendell, MD
role: STUDY_CHAIR
References:
citation: 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.