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A Phase I/IB Study of OSI-906 and Irinotecan in Patients With Advanced Cancer With Expanded Cohorts of Patients With Colorectal Cancer Stratified by the OSI-906 Integrated Classifier

Phase 1
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

A Phase I/IB Study of OSI-906 and Irinotecan in Patients With Advanced Cancer With Expanded Cohorts of Patients With Colorectal Cancer Stratified by the OSI-906 Integrated Classifier

This study plans to learn more about an investigational drug called OSI-906. OSI-906 is
being looked at to see if it could be a treatment for advanced cancer.

Subjects will also receive a drug called irinotecan (also called Camptosar®). This drug is
FDA approved for the treatment of metastatic colon cancer and some other types of cancer.
The study drug and irinotecan have never been tested together in humans. It is unknown if
the combination will be safe and/or effective in the treatment of human cancers.

The purpose of this study is to find the answers to the following research questions:

- What is the highest dose of the study drug that can be given to subjects in combination
with irinotecan without causing side effects that are too severe?

- How is the combination of the study drug and irinotecan handled in the blood of
subjects with advanced cancer? Does either the study drug or irinotecan have an effect
on how the other works?

- What are the most common side effects of the study drug and irinotecan when given
together to subjects with advanced cancer?

- Is the combination of the study drug and irinotecan effective in stopping the growth or
shrinking the size of your tumor?

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 >60mL/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

- 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

- 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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) and the recommend phase II dose (RP2D) for the combination of irinotecan and OSI-906 in patients with advanced cancer.

Outcome Time Frame:

Up to 28 days of treatment

Safety Issue:


Principal Investigator

Stephen Leong, M.D

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Colorado, Denver


United States: Food and Drug Administration

Study ID:



Start Date:

December 2009

Completion Date:

April 2013

Related Keywords:

  • Colorectal Cancer
  • OSI-906, irinotecan, colorectal cancer
  • Colorectal Neoplasms



University of Colorado DenverDenver, Colorado  80262