Study of Nimotuzumab and Irinotecan in Metastatic Colorectal Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Nimotuzumab Humanized Monoclonal Antibody; Drug: Nimotuzumab

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Dr. H. Bliss Purphy Cancer Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Hospital
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Mississauga, Ontario, Canada, L5M 2N1
      • Credit Valley Hospital /Carlo Fidani Peel Regional Cancer Centre
    • Newmarket, Ontario, Canada
      • Cancer Care Program Southlake Regional Health Centre
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre
    • Sault Ste Marie, Ontario, Canada, P6A 2C4
      • Algoma District Cancer Care Program
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Regional Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2; Nimotuzumab 400mg every week or every two weeks	Drug: Nimotuzumab Humanized Monoclonal Antibody; Nimotuzumab 400mg every week; Drug: Nimotuzumab; Nimotuzumab 400mg every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: YM BioSciences
• Investigators: Study Chair: Amil Shah, MD, Vancouver Cancer Centre BC cancer Agency

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ANTICIPATED): December 1, 2008

Study Registration Dates

• First Submitted: June 27, 2007
• First Submitted That Met QC Criteria: June 27, 2007
• First Posted (ESTIMATE): June 28, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): November 17, 2008
• Last Update Submitted That Met QC Criteria: November 14, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Colorectal cancer; Anti-EGFR
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies; Antibodies, Monoclonal; Nimotuzumab
• Other Study ID Numbers: YMB 1000-015