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

This study has been completed.
Sponsor:
Collaborator:
Australasian Gastro-Intestinal Trials Group
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00079066
First received: March 8, 2004
Last updated: October 31, 2013
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Quality of Life
Biological: cetuximab
Procedure: quality-of-life assessment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Objective response rate [ Designated as safety issue: No ]
  • Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire -C30 (EORTC QLQ-C30) [ Designated as safety issue: No ]
  • Health utilities by Health Utilities Index 13 (HU 13) [ Designated as safety issue: No ]
  • Economic evaluation [ Designated as safety issue: No ]
  • Safety profile [ Designated as safety issue: Yes ]

Study Start Date: August 2003
Study Completion Date: February 2009
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00079066

  Show 33 Study Locations
Sponsors and Collaborators
NCIC Clinical Trials Group
Australasian Gastro-Intestinal Trials Group
Investigators
Study Chair: Derek Jonker, MD Ottawa Regional Cancer Centre
Study Chair: Chris Karapetis, MD NHMRC Clinical Trials Centre
  More Information

Additional Information:
Publications:
Jonker DJ, Karapetis C, Harbison C, et al.: High epiregulin (EREG) gene expression plus K-ras wild-type (WT) status as predictors of cetuximab benefit in the treatment of advanced colorectal cancer (ACRC): results from NCIC CTG CO.17—A phase III trial of cetuximab versus best supportive care (BSC).. [Abstract] J Clin Oncol 27 (Suppl 15): A-4016, 2009.
Powell ED, Asmis T, Jonker D, et al.: Comorbidity and overall survival (OS) in cetuximab-treated patients with advanced colorectal cancer (ACRC)—results from NCIC CTG CO.17: A phase III trial of cetuximab versus best supportive care (BSC). [Abstract] J Clin Oncol 27 (Suppl 15): A-4074, 2009.
Mittmann N, Au HJ, Tu D, et al.: A prospective economic analysis of cost-effectiveness of cetuximab for metastatic colorectal cancer patients from the NCIC CTG and AGITG CO.17 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-6528, 2008.
O'Callaghan CJ, Tu D, Karapetis CS, et al.: The relationship between the development of rash and clinical and quality of life outcomes in colorectal cancer patients treated with cetuximab in NCIC CTG CO.17. [Abstract] J Clin Oncol 26 (Suppl 15): A-4130, 2008.
Au H, Karapetis C, Jonker D, et al.: Quality of life in patients with advanced colorectal cancer treated with cetuximab: results of the NCIC CTG and AGITG CO.17 trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-4002, 2007.
Jonker DJ, Karapetis CS, Moore M, et al.: Randomized phase III trial of cetuximab monotherapy plus best supportive care (BSC) versus BSC alone in patients with pretreated metastatic epidermal growth factor receptor (EGFR)-positive colorectal carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the Australasian Gastro-Intestinal Trials Group (AGITG). [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. 2007.

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00079066     History of Changes
Other Study ID Numbers: CO17, CAN-NCIC-CO17, AGITG-CAN-NCIC-CO17, BMS-CA225-025, IMCL-CAN-NCIC-CO17, CDR0000353486
Study First Received: March 8, 2004
Last Updated: October 31, 2013
Health Authority: United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:
quality of life
stage IV colon cancer
recurrent colon cancer
recurrent rectal cancer
stage IV rectal cancer

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
Mitogens
Cetuximab
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014