A Phase II Open-Label, 2-Cohort Study of Nimotuzumab 400 mg Weekly Plus Irinotecan (Cohort 1) and Nimotuzumab 400 mg Every 2 Weeks Plus Irinotecan (Cohort 2) in Patients With Irinotecan-Refractory Metastatic Colorectal Cancer
- Confirmed colorectal cancer with metastatic disease documented on diagnostic imaging
- Measurable disease,
- Must have clinical documentation of failure after receiving at least one chemotherapy
regimen for metastatic disease that contained irinotecan.
- Must have documentation of failure by CT, MRI or PET scan. Patients who were
intolerant of irinotecan despite dose attenuations are not eligible for this trial.
- Patients must have failed irinotecan which they received on one of the following
three starting regimens:Weekly,Biweekly or every 3 weeks. mg/m2.
6.Patients may have received any number of prior standard and investigational
regimens or radiation treatments, provided that they meet all other eligibility
- Age greater than 18 years.
- Life expectancy of greater than 3 months.
- ECOG performance status less than 1
- Patients must have normal organ and marrow function
- Patients must have medical documentation of dose, schedule, and dates of last
- Women of child-bearing potential and men must agree to use adequate contraception
- Patients must have the ability to understand and the willingness to sign a written
informed consent document.
Subject Exclusion Criteria
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
Neurotoxicity, if present, must have recovered to < grade 2.
- No other investigational agents.
- No known brain metastases.Patients with a history of primary CNS tumours, seizures
not well controlled with standard medical therapy, or history of stroke will also be
- History of allergic reactions attributed to compounds of chemical or biologic
composition similar to nimotuzumab, irinotecan, or other agents used in the study.
- Previous EGFR-directed therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring parenteral antibiotics, symptomatic congestive heart failure,
unstable angina pectoris, uncontrolled hypertension, clinically significant cardiac
arrhythmia, history of myocardial infarction within the past 6 months, or psychiatric
illness/social situations that would limit compliance with study requirements.
- HIV-positive patients on combination antiretroviral therapy are ineligible
- Active cardiovascular disease, e.g., uncontrolled hypertension, unstable angina, New
York Heart Association grade II or greater congestive heart failure, serious cardiac
arrhythmia requiring medications, or grade II or greater peripheral vascular disease.
In addition, patients with arterial thrombosis, myocardial infarction, and cerebral
vascular accidents [stroke/transient ischemic attack (TIA)] within 6 months prior to
study entry will be excluded.
- Organ allografts requiring immunosuppressive therapy. -.Pregnant or lactating women
are excluded from this study.