Clinical trial NCT01016860 (phase 1, status: terminated)
Conditions: colorectal cancer
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: osi-906, irinotecan
SMILES: C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1, CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O
Reason stopped: 
    this study was discontinued due to a shown lack of efficacy in the investigational agent
  
Eligibility criteria:

        Inclusion Criteria:

        • Dose Escalation Phase: Histological or cytopathological diagnosis of an advanced cancer
        that is refractory to standard therapy or for which no standard therapy exists.

        Irinotecan must be listed in the Compendia for reimbursement, ie. colorectal cancer; lung
        cancer; gastric; esophageal, cervical and ovarian cancer.

          -  Cohort Expansion Phase: Histological or cytopathological diagnosis of advanced
             colorectal cancer with known Kirsten rat sarcoma (KRAS) mutation status. All patients
             must have received and progressed or be intolerable of first-line therapy with an
             oxaliplatin-containing regimen. Patients must be screened using the OSI-906 integrated
             classifier.

          -  Cohort 1 (12 patients): Window of opportunity cohort: Patients with a score of at
             least 4 out of 5 by the OSI-906 integrated classifier who are irinotecan-naive will
             receive OSI-906 as a single agent until disease progression. Patients must be non
             surgically resectable or not a surgical candidate because of comorbid conditions. At
             disease progression, if the patient had a best response of at least stable disease for
             3 cycles (9 weeks), irinotecan may be added to OSI-906.

          -  Cohort 2: (16 patients: 8 KRAS wild-type (WT) and 8 KRAS Mutant(MT). Patients who have
             score of less than 4 by the OSI-906 integrated classifier will have OSI-906 added to
             irinotecan on disease progression to irinotecan (patients that are KRAS WT will have
             received cetuximab with irinotecan). Patients who are treated in the dose escalation
             phase at the recommended phase II dose of the combination and meet the criteria for
             Cohort 2 of the expanded phase may be counted towards the dose expansion patient
             numbers.

          -  Age ≥18 years old

          -  Patients must have an Eastern Co-operative oncology group (ECOG) performance status of
             0-1

          -  Life expectancy of at least three months.

          -  Adequate hematological function and bone marrow reserve:

        Hematopoetic: Neutrophil count ≥ 1.5 x 109/L (1,500/mm3), Platelet count ≥ 75 x 109/L,
        Hemoglobin ≥ 9.0g/dL

          -  Adequate hepatic and renal function Aspartate transaminase (AST) and alanine
             transaminase (ALT) ≤ 2.5 fold upper limit of normal (ULN) Bilirubin ≤ 1.5 X ULN
             Creatinine ≤ 1.5 fold ULN or calculated creatinine clearance, using the
             Cockcroft-Gault formula > 60 mL/min, if just below 60 mL/min then Glomerular
             Filtration Rate > 60 mL/min as determined by 24 hour urine collection

          -  Measurable (according to Response Evaluation Criteria in Solid Tumors (RECIST)
             Criteria in the dose expansion cohorts or measurable /evaluable disease in the Dose
             Escalation phase,

          -  Ability to understand the requirements of the study, provide written informed consent
             and comply with the study protocol procedures.

        A: Documentation of KRAS status must be performed prior to enrollment.

        Exclusion Criteria:

          -  Concurrent symptomatic central nervous system involvement, brain or meningeal
             metastases

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, unstable
             cardiac arrhythmia, uncontrolled diabetes, uncontrollable hypertension or psychiatric
             illness/social situations that would limit compliance with study requirements

          -  Documented history of diabetes

          -  Corrected QT (QTc) interval > 450 msec at baseline

          -  Drugs with a Risk of Causing corrected QT interval Prolongation: Drugs that have a
             risk of causing QT interval prolongation are prohibited within 14 days prior to Day 1
             dosing and while on study to avoid exacerbation of any OSI-906 potential side effects

          -  Known positive serology for the human immunodeficiency virus (HIV), Hepatitis B and/or
             Hepatitis C

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
             bowel disease), or significant bowel resection that would preclude adequate absorption

          -  Gastrointestinal tract disease (including peptic ulcer disease) or prior surgery
             resulting in an inability to take oral medications

          -  Patients may have had prior therapy, providing the following conditions are met:

        Chemotherapy: A minimum of 3 weeks (4 weeks for carboplatin or investigational anticancer
        agents and 6 weeks for nitrosoureas and mitomycin C) must have elapsed between the end of
        treatment and start of treatment. Patients must have recovered from any treatment-related
        toxicities (except for alopecia, fatigue, and grade 1 neurotoxicity) prior to start of
        treatment.

        Hormonal therapy: Patients may have had prior anticancer hormonal therapy provided it is
        discontinued prior to start of treatment. However, patients with prostate cancer with
        evidence of progressive disease may continue on therapy that produces medical castration
        (eg, goserelin or leuprorelin), provided this therapy was commenced at least 3 months
        earlier.

        Radiation: Patients may have had prior radiation therapy provided they have recovered from
        the acute, toxic effects of radiotherapy prior to start of treatment. A minimum of 21 days
        must have elapsed between the end of radiotherapy and start of treatment if the radiation
        affected more than 25% of bone marrow otherwise a 14 days wash out is required.

        Surgery: Previous surgery is permitted provided that wound healing has occurred prior to
        start of treatment.

        • Laboratory results: international normalized ratio (INR) ≥ 1.5 X ULN and activated
        partial thromboplastin time (aPTT) ≥ 1.5 X ULN

        Fasting blood glucose of >125mg/dL at baseline and on Day 1 of dosing.

          -  Women who are pregnant or breast feeding because of teratogenic potential.

          -  Women of childbearing potential in whom pregnancy cannot be excluded or who are not
             using an adequate method of contraception because of teratogenic potential.

          -  Prior documented hypersensitivity to irinotecan