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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00079066
• Other study ID #: CO17
• Secondary ID: CAN-NCIC-CO17AGI
• Status: Completed
• Phase: Phase 3
• Start date: December 30, 2003
• Est. completion date: February 10, 2009

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 572
• Est. completion date: February 10, 2009
• Est. primary completion date: November 3, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Quality of Life

Intervention

Biological:
• cetuximab

Procedure:
• quality-of-life assessment

Locations

Country	Name	City	State
Australia	NHMRC Clinical Trials Centre	Camperdown	New South Wales
Canada	Belleville General Hospital	Belleville	Ontario
Canada	Prince Edward Island Cancer Centre at Queen Elizabeth Hospital	Charlottetown	Prince Edward Island
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Grand River Regional Cancer Centre at Grand River Hospital	Kitchener	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Hopital Du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador
Canada	Fraser Valley Cancer Centre at British Columbia Cancer Agency	Surrey	British Columbia
Canada	Northwestern Ontario Regional Cancer Care at Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	St. Joseph's Health Centre - Toronto	Toronto	Ontario
Canada	St. Michael's Hospital - Toronto	Toronto	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Australasian Gastro-Intestinal Trials Group

Countries where clinical trial is conducted

Australia,  Canada, 

References & Publications (9)

Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results fr — View Citation

Au HJ, Karapetis CS, O'Callaghan CJ, Tu D, Moore MJ, Zalcberg JR, Kennecke H, Shapiro JD, Koski S, Pavlakis N, Charpentier D, Wyld D, Jefford M, Knight GJ, Magoski NM, Brundage MD, Jonker DJ. Health-related quality of life in patients with advanced colore — View Citation

Gupta A, O'Callaghan CJ, Zhu L, Jonker DJ, Wong RPW, Colwell B, Moore MJ, Karapetis CS, Tebbutt NC, Shapiro JD, Tu D, Booth CM. Evaluating the Time Toxicity of Cancer Treatment in the CCTG CO.17 Trial. JCO Oncol Pract. 2023 Jun;19(6):e859-e866. doi: 10.1200/OP.22.00737. Epub 2023 Mar 7. — View Citation

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

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

Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. — View Citation

Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal can — View Citation

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, 2

Outcome

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