Monoclonal Antibody Therapy Compared With No Further Therapy After Surgery in Treating Patients With Stage II Colon Cancer - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborators:	National Cancer Institute (NCI) Southwest Oncology Group Eastern Cooperative Oncology Group North Central Cancer Treatment Group European Organization for Research and Treatment of Cancer - EORTC NCIC Clinical Trials Group
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00002968

Purpose

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	Intervention	Phase
Colorectal Cancer	Biological: edrecolomab	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase III Randomized Study of Adjuvant Immunotherapy With Monoclonal Antibody 17-1A Versus No Adjuvant Therapy Following Resection for State II (Modified Astler-Coller B2) Adenocarcinoma of the Colon

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Monoclonal antibody 17-1A Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment:	1738
Study Start Date:	May 1997
Study Completion Date:	June 2010
Primary Completion Date:	July 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Monoclonal antibody adjuvant therapy Treatment with monoclonal antibody post surgery	Biological: edrecolomab 500mg edrecolomab in NS IV infusion over 2 hours one time in wk 1; then 100 mg edrecolomab in NS infusion over 2 hours one time in wks 5,9,13,and 17 Other Name: 17-1A
No Intervention: Standard Care treatment

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002968

Locations

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

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Southwest Oncology Group

Eastern Cooperative Oncology Group

North Central Cancer Treatment Group

European Organization for Research and Treatment of Cancer - EORTC

NCIC Clinical Trials Group

Investigators

Study Chair:	Thomas A. Colacchio, MD	Norris Cotton Cancer Center
Study Chair:	S. G. Eckhardt, MD	University of Colorado, Denver
Study Chair:	Al B. Benson, MD, FACP	Robert H. Lurie Cancer Center
Study Chair:	Richard M. Goldberg, MD	Mayo Clinic
Study Chair:	Philippe Rougier, MD	Hopital Ambroise Pare
Study Chair:	Anthony L.A. Fields, MD, FRCPC	Cross Cancer Institute at University of Alberta

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Bertagnolli MM, Niedzwiecki D, Hall M, et al.: Presence of 18q loss of heterozygosity (LOH) and disease-free and overall survival in stage II colon cancer: CALGB Protocol 9581. [Abstract] J Clin Oncol 27 (Suppl 15): A-4012, 2009.

Colacchio TA, Niedzwiecki D, Compton C, et al.: Phase III trial of adjuvant immunotherapy with MOAb 17-1A following resection for stage II adenocarcinoma of the colon (CALGB 9581). [Abstract] J Clin Oncol 22 (Suppl 14): A-3522, 250s, 2004.

Responsible Party:	Monica M Bertagnolli, MD, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00002968 History of Changes
Other Study ID Numbers:	CDR0000065473, U10CA031946, CLB-9581, CAN-NCIC-CO14, E-C9581, EORTC-40991, NCCTG-C9581, SWOG-C9581
Study First Received:	November 1, 1999
Last Updated:	August 3, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:

stage II colon cancer
adenocarcinoma of the colon

Additional relevant MeSH terms:

Adenocarcinoma
Colonic Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases

Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Monoclonal antibody 17-1A
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012