Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI NCCTG-N0147 ECOG-N0147, N0147, NCT00079274

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Compare the disease-free survival of patients with curatively resected stage III colon cancer treated with adjuvant irinotecan vs oxaliplatin with fluorouracil and leucovorin calcium vs both regimens given consecutively (all irinotecan-containing treatment arms are closed to accrual as of 6/1/2005).
2. Compare the disease-free survival of patients treated with these regimens with vs without cetuximab.

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Compare the disease-free and overall survival of patients whose tumors express epidermal growth factor receptor treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the quality of life, measures of patient satisfaction, nutrition, and cancer risk in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the colon
  • Stage III disease
  • No resected stage IV disease



• No rectal cancer
  • Gross inferior (caudad) margin of the primary tumor must be ≥ 12 cm from the anal verge by rigid proctoscopy



• Stage III tumor must have been completely resected within the past 56 days
  • Must have documented en bloc resection in patients with tumor adherence to adjacent structures
  • Tumor-related obstructions and colonic perforation are allowed
  • Tumor samples must be available



• At least 1 pathologically confirmed positive lymph node
  • No evidence of residual involved lymph node disease



• Synchronous primary colon cancer allowed



• No distant metastatic disease

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent biologic therapy
• No concurrent oprelvekin
• No concurrent pegfilgrastim

Chemotherapy

• No prior chemotherapy for colon cancer
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for colon cancer

Surgery

• See Disease Characteristics

Other

• No prior agents directed against epidermal growth factor-receptor
• No concurrent ketoconazole or other potent inhibitors of CYP3A4 (e.g., itraconazole or voriconazole)
• No other concurrent anticancer therapy
• No concurrent targeted agents

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No uncontrolled high blood pressure
• No unstable angina
• No symptomatic congestive heart failure
• No myocardial infarction with the past 6 months
• No New York Heart Association class III or IV heart disease

Pulmonary

• No symptomatic pulmonary fibrosis
• No symptomatic interstitial pneumonitis

Immunologic

• No prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy
• No known allergy to platinum compounds
• No documented presence of human anti-mouse antibodies (HAMA)
• No active uncontrolled bacterial, viral, or systemic fungal infection
• HIV negative
• No clinically defined AIDS

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation
• No inadequately treated gastrointestinal bleeding
• No ≥ grade 2 pre-existing peripheral sensory or motor neuropathy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or lobular carcinoma in situ in 1 breast
• No other concurrent medical condition that would preclude study participation

Expected Enrollment

A total of 2,648 patients will be accrued for this study.

Outcomes

Disease-free survival at 3 years

Overall survival

Outline

This is a randomized, multicenter study. Patients are stratified according to positive lymph node involvement (1-3 vs 4 or more), histology (high [poorly differentiated or undifferentiated] vs low [well to moderately differentiated]), and clinical T stage (T1 or T2 vs T3 vs T4). Patients are randomized to 1 of 6 treatment arms (as of 6/1/2005, patients are randomized to treatment arms I and IV only; arms II, III, V, and VI are closed to accrual).

• Arm I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.



• Arm II (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.



• Arm III (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive the same treatment as in arm I for 6 courses followed by the same treatment as in arm II for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.



• Arm IV: Patients receive cetuximab* IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.



• Arm V (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and irinotecan, leucovorin calcium, and fluorouracil as in arm II. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.



• Arm VI (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and chemotherapy as in arm III.

   [Note: *Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only.]

Quality of life is assessed at baseline, before course 6, and at the end of therapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 3 years.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Steven Alberts, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Albert Bernath, MD, Protocol co-chair		Ph: 570-214-9290
Frank Sinicrope, MD, Principal investigator		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Eastern Cooperative Oncology Group

Gershon Locker, MD, FACP, Protocol chair		Ph: 847-570-2515; 888-909-5222 Email: gylocker@northwestern.edu

U.S.A.
Alabama
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700 800-333-1305
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Castro Valley
	East Bay Radiation Oncology Center
		James Feusner, MD	Ph:  510-428-3689
	Eden Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Fresno
	California Cancer Center - Woodward Park Office
		Dina Ibrahim	Ph:  559-451-3647
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5085
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Orange
	St. Joseph Hospital Regional Cancer Center - Orange
		Edward Alexson	Ph:  714-771-8999
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-2596
	San Francisco
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Walnut Creek
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph:  970-212-7600
	Poudre Valley Hospital
		Clinical Trials Office - Poudre Valley Hospital	Ph:  970-495-8226
Connecticut
	Hartford
	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
		Jonathan Sporn, MD	Ph:  860-714-4680
	Manchester
	Manchester Memorial Hospital
		Jeffrey Wasser, MD	Ph:  860-646-0670
	Norwich
	Eastern Connecticut Hematology and Oncology Associates
		Dennis Slater, MD	Ph:  860-886-8362
Delaware
	Dover
	Kent General Hospital
		Iftekhar Khan, MD	Ph:  302-674-4700
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
Florida
	Boca Raton
	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
		Clinical Trials Office - Eugene M. and Christine E. Lynn Cancer Institute	Ph:  561-955-4800
	Daytona Beach
	Herbert D. Kerman Regional Oncology Center - Daytona Beach
		Ruby Anne Deveras	Ph:  386-254-4211
	Fort Lauderdale
	Broward General Medical Center Cancer Center
		Clinical Trials Office - Broward General Medical Center Cancer Center	Ph:  954-355-5346
	Gainesville
	University of Florida Shands Cancer Center
		Clinical Trials Office - University of Florida Shands Cancer Center	Ph:  888-254-7581
	Lakeland
	Center for Cancer Care and Research at Watson Clinic, LLP
		Clinical Trials Office - Center for Cancer Care and Research	Ph:  863-680-7780
	Orange Park
	Integrated Community Oncology Network - Orange Park
		Linda Struhar-Sylvester, MD, FACP	Ph:  904-272-3139
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clinical Trials Office - Florida Hospital Cancer Institute	Ph:  407-303-5623
	Sarasota
	Florida Cancer Specialists - Sarasota Downtown
		Clinical Trials Office - Florida Cancer Specialists - Sarasota Downtown	Ph:  941-957-1000 ext. 213
	Stuart
		Alpana Desai	Ph:  772-223-5952
	Robert and Carol Weissman Cancer Center at Martin Memorial
		Alpana Desai	Ph:  772-223-5952
	West Palm Beach
	Palm Beach Cancer Institute - West Palm Beach
		Robert Green, MD	Ph:  561-366-4117
Georgia
	Albany
	Phoebe Cancer Center at Phoebe Putney Memorial Hospital
		Clinical Trials Office - Phoebe Cancer Center	Ph:  229-312-2251
	Augusta
	Augusta Oncology Associates - Walton Way
		Mark Keaton, MD	Ph:  706-821-2944
	Gainesville
	Northeast Georgia Medical Center
		Richard LoCicero, MD	Ph:  770-535-3553
	Savannah
	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
		Mark Taylor, MD	Ph:  912-819-6194voicemail
	Valdosta
	Pearlman Comprehensive Cancer Center at South Georgia Medical Center
		Contact Person	Ph:  229-259-4600
Illinois
	Alton
	Saint Anthony's Hospital at Saint Anthony's Health Center
		Bethany Sleckman, MD	Ph:  314-251-6573
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-6601
	Evanston
	St. Francis Hospital
		K. Joseph Philip, MD	Ph:  847-869-2076
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Sanjiv Modi	Ph:  815-730-3098
	Kankakee
	Provena St. Mary's Regional Cancer Center - Kankakee
		David Debono, MD	Ph:  815-937-8780
	La Grange
	La Grange Memorial Hospital
		Clinical Trials Office - La Grange Memorial Hospital	Ph:  630-856-7526
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-6573
	Naperville
	Edward Hospital Cancer Center
		Clinical Trials Office - Edward Hospital Cancer Center	Ph:  630-646-6075
	Oak Lawn
	Advocate Christ Medical Center
		Thomas M. Hoeltgen, MD	Ph:  708-424-9710
	Rockford
	Swedish-American Regional Cancer Center
		Clinical Trials Office - Swedish-American Regional Cancer Center	Ph:  815-489-4413
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard Gross, MD	Ph:  317-787-3311
	Elkhart
	Elkhart General Hospital
		Rafat Ansari, MD, FACP	Ph:  574-234-5123
	Indianapolis