Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
Novartis Pharmaceuticals
OSI Pharmaceuticals
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01154335
First received: June 29, 2010
Last updated: January 6, 2015
Last verified: January 2015

June 29, 2010
January 6, 2015
July 2010
May 2013   (final data collection date for primary outcome 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. [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
To determine the maximum tolerated dose of the combination of OSI-906 and everolimus for the treatment of patients with refractory metastatic colorectal cancer. [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01154335 on ClinicalTrials.gov Archive Site
  • Progression-Free Survival (PFS) [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the time between Day 1 Cycle 1 and date of first documented recurrence or death. Patients who do not exhibit progression while on trial will be censored at their last known assessment. Progression is defined per RECIST criteria as either 1) at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions. Requires not only 20% increase, but absolute increase of a minimum of 5 mm over sum. OR 2) Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
  • Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time between Day 1 Cycle 1 to the date of death from any cause. Those remaining alive will be censored at their last known assessment or follow-up.
  • Response Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Response rate (RR) will be estimated as the proportion of patients exhibiting complete response or partial response out of all evaluable cases. Complete Response is defined per RECIST as disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Efficacy of the combination of OSI-906 and everolimus by measurement of progression-free survival (PFS), response rate (RR), and overall survival (OS) in the treatment of patients with refractory metastatic colorectal cancer. [ Time Frame: 18 Months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Everolimus and OSI-906 for Patients With Refractory Metastatic Colorectal Cancer
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Colorectal Cancer
  • Drug: 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
  • 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
  • Experimental: 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

    Interventions:
    • Drug: OSI-906
    • Drug: Everolimus
  • Experimental: 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

    Interventions:
    • Drug: OSI-906
    • Drug: Everolimus
  • Experimental: 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

    Interventions:
    • Drug: OSI-906
    • Drug: Everolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
May 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01154335
SCRI GI 124
No
SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
  • Novartis Pharmaceuticals
  • OSI Pharmaceuticals
Study Chair: Johanna Bendell, MD SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP