Study of Nimotuzumab and Irinotecan in Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00493857
• Other study ID #: YMB 1000-015
• Status: Terminated
• Phase: Phase 2
• First received: June 27, 2007
• Last updated: November 14, 2008
• Start date: June 2007
• Est. completion date: December 2008

Study information

• Verified date: November 2008
• Source: YM BioSciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This study will determine if nimotuzumab provides a benefit in this type of cancer when given in combination with irinotecan.

The study will test:

• How long any good effects last.

• How bad any side effects are.

Objectives:

Primary:

The primary goal is to assess the Objective Response Rate (ORR) that the combination of irinotecan and nimotuzumab will produce in patients with irinotecan-refractory metastatic colorectal cancer

Secondary:

• To assess the incidence of Grade 2 or greater acneiform rash or infusion reaction, allergic reaction or anaphylactoid reaction AEs in patients with irinotecan-refractory metastatic colorectal cancer following weekly or 2-weekly nimotuzumab schedules;

• To assess Progression-Free Survival (PFS), defined as time from date of randomization until date of disease progression (clinical or radiological) or death due to any cause, for the two nimotuzumab schedules;

• To assess the rates and durations of Stable Disease (SD) following weekly or 2-weekly nimotuzumab schedules;

• To assess the Time to Disease Progression (TTP) following weekly or 2-weekly nimotuzumab schedules;

• To evaluate ORR in patients who are identified as having "primary" irinotecan resistance following weekly or 2-weekly nimotuzumab schedules;

• To evaluate Overall Survival (OS) following weekly or 2-weekly nimotuzumab schedules;

• To compare the two dosing schedules of nimotuzumab with respect to objective response rates and safety;

• To evaluate the overall safety and toxicity profiles of these two dose regimens of nimotuzumab;

• To evaluate trough levels and accumulation of nimotuzumab in serum of patients receiving the drug on weekly or 2-weekly regimens.

Description:

The patient will receive nimotuzumab every 2 weeks plus irinotecan. Nimotuzumab will be given at a dose of 400 mg once every 2 weeks for 12 weeks. Irinotecan will be given at the same dose and schedule as the last dose and schedule given during the most recent pre-study irinotecan containing therapy. If the tumour does not show signs of further growth after 12 weeks of treatment, the patient will continue receiving nimotuzumab 400 mg every 2 weeks for up to 18 months or as long as they are getting a benefit from the drug.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: December 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Confirmed colorectal cancer with metastatic disease documented on diagnostic imaging studies.

• 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 criteria.

• 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 irinotecan administration.

• 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 excluded.

• 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.

Study Design

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Nimotuzumab Humanized Monoclonal Antibody
Nimotuzumab 400mg every week
• Nimotuzumab
Nimotuzumab 400mg every 2 weeks

Locations

Country	Name	City	State
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Grand River Hospital	Kitchener	Ontario
Canada	London Regional Cancer Centre	London	Ontario
Canada	Credit Valley Hospital /Carlo Fidani Peel Regional Cancer Centre	Mississauga	Ontario
Canada	Cancer Care Program Southlake Regional Health Centre	Newmarket	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Algoma District Cancer Care Program	Sault Ste Marie	Ontario
Canada	Dr. H. Bliss Purphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
YM BioSciences

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary goal is to assess the Objective Response Rate (ORR) that the combination of irinotecan and nimotuzumab will produce in patients with irinotecan-refractory metastatic colorectal cancer		18-24 months
Secondary	Assess the incidence of acneiform rash,drug reaction,adverse events, the assessment of progression-free survival,stable disease,time to disease progression, overall survival, objective response rates, safety and trough levels in the serum of patients.		18-24 months	Yes