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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00079066

Collaborator

Australasian Gastro-Intestinal Trials Group (Other)

572

Enrollment

Locations

65.5

Actual Duration (Months)

17.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

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

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 Design

Study Type:

Interventional

Actual Enrollment :

572 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Start Date :

Aug 28, 2003

Actual Primary Completion Date :

Nov 3, 2006

Actual Study Completion Date :

Feb 10, 2009

Outcome Measures

Primary Outcome Measures

Overall survival []

Secondary Outcome Measures

Time to progression []
Objective response rate []
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) []
Economic evaluation []
Safety profile []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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