RATIONALE: Monoclonal antibodies such as edrecolomab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether surgery to remove colon cancer is more effect with or without monoclonal antibody therapy.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without monoclonal antibody therapy in treating patients who have stage II colon cancer.

Condition	Treatment or Intervention	Phase
stage II colon cancer adenocarcinoma of the colon	Drug: edrecolomab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Determine whether adjuvant therapy with edrecolomab improves the probability of survival and disease-free survival and increases disease-free intervals in patients who have undergone resection for stage II colon cancer.
• Determine whether alterations in the expression cell cycle related genes predict the risk of survival or recurrence in this patient population.
• Determine whether alterations in markers of metastatic potential such as expression of the "Deleted in Colon Cancer" (DCC) gene, and measures of tumor angiogenesis predict the risk of survival and recurrence in these patients.
• Determine whether markers of cellular differentiation (e.g., sucrase isomaltase) predict the risk of survival or recurrence in these patients.
• Determine whether DNA ploidy and cell proliferation are prognostic of tumor recurrence and overall survival in stage II colon cancer.
• Determine whether interactions among these tumor markers identify subsets of patients with significantly altered outcomes.
• Determine whether pathologic features including tumor grade, tumor mitotic (proliferation) index, tumor border configuration, and host lymphoid response to tumor and lymphatic, venous, and perineural invasion predict outcome in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to degree of differentiation (well vs moderately well vs poor), vascular or lymphatic invasion (no vs yes), and preoperative serum CEA (less than 5.0 ng/mL vs at least 5.0 ng/mL vs unknown). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive adjuvant edrecolomab IV over 2 hours on day 1. Treatment repeats every 28 days for 5 courses. Patients must begin therapy no earlier than 7 days and no later than 42 days postsurgical resection. Patients also undergo observation at 3 and 6 months postrandomization.
• Arm II: Patients undergo observation at 3 and 6 months postrandomization. Patients are followed after the last course of edrecolomab (arm I) and at 12 months (arm II). All patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 2,100 patients will be accrued for this study within 4.7 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically proven adenocarcinoma of the colon (Stage II pT3, N0 or pT4b, N0, excluding pT4a, N0)
• With or without penetration of the serosa
• No lymph node metastases
• No distant metastases or penetration of adjacent structures/organs
• Proximal, distal, and radial margins must be tumor free
• A minimum of three (optimal of 6) nodes (pericolic or mesenteric) are required for evaluation
• Complete en bloc resection of all primary tumors (not performed or assisted by laparoscopic methods)
• No evidence of perforation or obstruction of the bowel
• Must be a colon, not a rectal, cancer
• More than one synchronous primary colon tumor allowed

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance Status:

• CALGB 0-1

Life Expectancy:

• More than 2 years

Hematopoietic:

• Granulocyte count greater than 1,800/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• BUN less than 1.5 times normal
• Bilirubin less than 1.5 times normal

Renal:

• Creatinine less than 1.5 times normal

Cardiovascular:

• No uncontrolled or severe cardiovascular disease

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior or concurrent malignancies within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
• No psychosis
• No history of pancreatitis

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior exposure to murine antibodies

Chemotherapy:

• No prior chemotherapy for adenocarcinoma of the colon
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent systemic steroids
• No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent corticosteroids, including replacement steroids for adrenal insufficiency
• Concurrent inhaled steroids in daily doses of 500 ug or less allowed
• Concurrent topical steroids allowed

Radiotherapy:

• No prior radiotherapy for adenocarcinoma of the colon

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Canada
      Lions Gate Hospital, North Vancouver,  V7L 2P9,  Canada
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, British Columbia
      British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna,  British Columbia,  V1Y 5L3,  Canada
      British Columbia Cancer Agency - Fraser Valley Cancer Centre, Surrey,  British Columbia,  V3V 1Z2,  Canada
      Nanaimo Cancer Clinic, Nanaimo,  British Columbia,  V9S 2B7,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, New Brunswick
      Doctor Leon Richard Oncology Centre, Moncton,  New Brunswick,  E1C 8X3,  Canada
      Moncton Hospital, Moncton,  New Brunswick,  E1C 6ZB,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Kingston Regional Cancer Centre, Kingston,  Ontario,  K7L 5P9,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Northeastern Ontario Regional Cancer Centre, Sudbury, Sudbury,  Ontario,  P3E 5J1,  Canada
      Northwestern Ontario Regional Cancer Centre, Thunder Bay, Thunder Bay,  Ontario,  P7A 7T1,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Peterborough Oncology Clinic, Peterborough,  Ontario,  K9H 7B6,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Scarborough Hospital - General Site, Scarborough,  Ontario,  M1P 2V5,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Prince Edward Island
      Queen Elizabeth Hospital, PEI, Charlottetown,  Prince Edward Island,  C1A 8T5,  Canada
Canada, Quebec
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada
      CHUM Hopital Saint-Luc, Montreal,  Quebec,  H2X 3J4,  Canada
      Complexe Hospitalier de la Sagamie, Chicoutimi,  Quebec,  G7H 5H6,  Canada
      Hopital Du Sacre-Coeur de Montreal, Montreal,  Quebec,  H4J 1C5,  Canada
      L'Hopital Laval, Ste Foy,  Quebec,  G1V 4G5,  Canada
      L'Hotel Dieu de Levis, Levis,  Quebec,  G6V 3Z1,  Canada
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

Thomas A. Colacchio, MD,  Study Chair,  Dartmouth-Hitchcock Medical Center   
S. Gail Eckhardt, MD,  Study Chair,  University of Colorado Cancer Center   
Al Bowen Benson, MD, FACP,  Study Chair,  Robert H. Lurie Cancer Center   
Richard M. Goldberg, MD,  Study Chair,  Mayo Clinic Cancer Center   
Philippe Rougier, MD,  Study Chair,  CHU Ambroise Pare   
Anthony L.A. Fields, MD, FRCPC,  Study Chair,  Cross Cancer Institute   

Study ID Numbers:  CDR0000065473; CLB-9581; CAN-NCIC-CO14; E-C9581; EORTC-40991; NCCTG-C9581; SWOG-C9581
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002968
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08