Study of Nimotuzumab and Irinotecan in Metastatic Colorectal Cancer

This study has been terminated.
(Cohort 2 not going forward. Manadate changes in Company)
Sponsor:
Information provided by:
YM BioSciences
ClinicalTrials.gov Identifier:
NCT00493857
First received: June 27, 2007
Last updated: November 14, 2008
Last verified: November 2008
  Purpose

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.

Condition Intervention Phase
Colorectal Cancer
Drug: Nimotuzumab Humanized Monoclonal Antibody
Drug: Nimotuzumab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by YM BioSciences:

Primary Outcome Measures:
  • 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 [ Time Frame: 18-24 months ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 18-24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: June 2007
Estimated Study Completion Date: December 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493857

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

No publications provided

ClinicalTrials.gov Identifier: NCT00493857     History of Changes
Other Study ID Numbers: YMB 1000-015
Study First Received: June 27, 2007
Last Updated: November 14, 2008
Health Authority: Canada: Health Canada

Keywords provided by YM BioSciences:
Colorectal cancer
Monoclonal antibody
Anti-EGFR

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Antibodies, Monoclonal
Irinotecan
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014