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	Treatment or Intervention	Phase
Quality of Life stage IV colon cancer recurrent colon cancer recurrent rectal cancer Stage IV rectal cancer	Drug: cetuximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: quality-of-life assessment  Procedure: supportive care/therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

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 or 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

• No 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

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

Study chairs or principal investigators

Derek Jonker, MD,  Study Chair,  Ottawa Regional Cancer Centre   
Chris Karapetis, MD,  Study Chair,  NHMRC Clinical Trials Centre   

Study ID Numbers:  CDR0000353486; CAN-NCIC-CO17; AGITG-CAN-NCIC-CO17; BMS-CA225-025; IMCL-CAN-NCIC-CO17; NCT00079066
Record last reviewed:  January 2005
Last Updated:  April 4, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079066
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08