Cetuximab + Best Supportive Care Compared With Best Supportive Care Alone in Metastatic Epidermal Growth Factor Receptor-Positive Colorectal Cancer

August 3, 2023 updated by: NCIC Clinical Trials Group

A Phase III Randomized Study of Cetuximab (Erbitux™, C225) and Best Supportive Care Versus Best Supportive Care in Patients With Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma

RATIONALE: Monoclonal antibodies, such as cetuximab, can target tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Best supportive care is the use of drugs and other treatments to improve the quality of life of patients. Combining cetuximab with best supportive care may slow the growth of the tumor and help patients live longer and more comfortably. It is not yet known whether cetuximab combined with best supportive care is more effective than best supportive care alone in treating metastatic epidermal growth factor receptor-positive colorectal cancer.

PURPOSE: This randomized phase III trial is studying cetuximab and best supportive care to see how well they work compared to best supportive care alone in treating patients with metastatic epidermal growth factor receptor-positive colorectal cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare survival of patients with metastatic epidermal growth factor receptor-positive colorectal cancer treated with cetuximab and best supportive care vs best supportive care alone.

Secondary

  • Compare the time to disease progression in patients treated with these regimens.
  • Compare the objective response rate in patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.
  • Compare the health utilities of patients treated with these regimens.
  • Conduct a comparative economic evaluation in patients treated with these regimens.
  • Determine the safety profile of cetuximab in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center and ECOG performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive an initial loading dose of cetuximab IV over 120 minutes on day 1. Patients continue to receive maintenance infusions of cetuximab IV over 60 minutes weekly. Patients also receive best supportive care, defined as measures designed to provide palliation of symptoms and improve quality of life as much as possible.
  • Arm II: Patients receive best supportive care as in arm I. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, and then at 4, 8, 16, and 24 weeks (or until deterioration to ECOG PS 4 or hospitalization for end-of-life care).

Patients are followed every 4 weeks.

PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this study within 20 months.

Study Type

Interventional

Enrollment (Actual)

572

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 1450
        • NHMRC Clinical Trials Centre
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute at University of Alberta
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 5L3
        • British Columbia Cancer Agency - Centre for the Southern Interior
      • Surrey, British Columbia, Canada, V3V 1Z2
        • Fraser Valley Cancer Centre at British Columbia Cancer Agency
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency - Vancouver Cancer Centre
      • Victoria, British Columbia, Canada, V8R 6V5
        • British Columbia Cancer Agency - Vancouver Island Cancer Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2H 2A6
        • CancerCare Manitoba
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6ZB
        • Moncton Hospital
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Saint John Regional Hospital
    • Newfoundland and Labrador
      • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
        • Newfoundland Cancer Treatment and Research Foundation
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
        • Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre
    • Ontario
      • Belleville, Ontario, Canada, K8N 5K5
        • Belleville General Hospital
      • Kingston, Ontario, Canada, K7L 5P9
        • Cancer Centre of Southeastern Ontario At Kingston General Hospital
      • Kitchener, Ontario, Canada, N2G 1G3
        • Grand River Regional Cancer Centre at Grand River Hospital
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program at London Health Sciences Centre
      • Oshawa, Ontario, Canada, L1G 2B9
        • R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital Regional Cancer Centre - General Campus
      • St. Catharines, Ontario, Canada, L2R 5K3
        • Hotel Dieu Health Sciences Hospital - Niagara
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
      • Toronto, Ontario, Canada, M4C 3E7
        • Toronto East General Hospital
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital - Toronto
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital - Toronto
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre
      • Toronto, Ontario, Canada, M6R 1B5
        • St. Joseph's Health Centre - Toronto
      • Windsor, Ontario, Canada, N8W 2X3
        • Windsor Regional Cancer Centre at Windsor Regional Hospital
    • Prince Edward Island
      • Charlottetown, Prince Edward Island, Canada, C1A 8T5
        • Prince Edward Island Cancer Centre at Queen Elizabeth Hospital
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Hopital Charles LeMoyne
      • Montreal, Quebec, Canada, H4J 1C5
        • Hôpital du Sacré-Coeur de Montréal
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill Cancer Centre at McGill University
      • Montreal, Quebec, Canada, H2L 4MI
        • Centre Hospitalier de l'Universite de Montreal
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre at Pasqua Hospital
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre at the University of Saskatchewan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal cancer

    • Metastatic disease
  • Epidermal growth factor receptor (EGFR)-positive by immunochemistry
  • Measurable or evaluable disease

  • Not amenable to standard curative therapy

    • Best supportive care is the only available option

  • Must have received a prior thymidylate synthase inhibitor (e.g., fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) in the adjuvant or metastatic setting

    • Combination therapy with oxaliplatin or irinotecan allowed
  • Must have failed* a prior regimen containing irinotecan and a prior regimen containing oxaliplatin for metastatic disease OR relapsed within 6 months after an adjuvant regimen containing irinotecan or oxaliplatin OR have documented unsuitability for such regimens
  • No symptomatic CNS metastases NOTE: *Failure is defined as either disease progression (clinical or radiological) or intolerance to the regimen

PATIENT CHARACTERISTICS:

Age

  • 16 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics
  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 8.0 g/dL

Hepatic

  • AST and ALT ≤ 5 times upper limit of normal (ULN)
  • Bilirubin ≤ 2.5 times ULN

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

  • No uncontrolled angina
  • No arrhythmias
  • No cardiomyopathy
  • No congestive heart failure
  • No myocardial infarction* within the past 6 months NOTE: *Pre-treatment ECG as only evidence of infarction is allowed

Pulmonary

  • No severe restrictive lung disease
  • No interstitial lung disease by chest x-ray

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment
  • No active pathological condition that would preclude study participation
  • No psychological or geographical condition that would preclude study compliance
  • No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior cetuximab
  • No prior murine monoclonal antibody therapy (e.g., edrecolomab)

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy and recovered
  • No concurrent chemotherapy

Radiotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered
  • Concurrent palliative radiotherapy allowed except to index lesions

Surgery

  • At least 4 weeks since prior major surgery and recovered

Other

  • No prior EGFR-targeted therapy (e.g., erlotinib or gefitinib)
  • More than 30 days since prior experimental therapeutic agents
  • More than 4 weeks since prior investigational agents
  • No concurrent enrollment in another clinical study
  • No other concurrent EGFR-targeted therapy
  • No other concurrent non-cytotoxic experimental agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival

Secondary Outcome Measures

Outcome Measure
Time to progression
Objective response rate
Safety profile
Economic evaluation
Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire -C30 (EORTC QLQ-C30)
Health utilities by Health Utilities Index 13 (HU 13)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Collaborators

Australasian Gastro-Intestinal Trials Group

Investigators

  • Study Chair: Derek Jonker, MD, Ottawa Regional Cancer Centre
  • Study Chair: Chris Karapetis, MD, National Health and Medical Research Council, Australia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 30, 2003

Primary Completion (Actual)

November 3, 2006

Study Completion (Actual)

February 10, 2009

Study Registration Dates

First Submitted

March 8, 2004

First Submitted That Met QC Criteria

March 8, 2004

First Posted (Estimated)

March 9, 2004

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO17
  • CAN-NCIC-CO17 (Other Identifier: PDQ)
  • AGITG-CAN-NCIC-CO17 (Other Identifier: AGITG)
  • BMS-CA225-025 (Other Identifier: Bristol-Myers Squibb)
  • IMCL-CAN-NCIC-CO17 (Other Identifier: ImClone Systems Incorporated)
  • CDR0000353486 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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