Radiation Therapy Before Surgery Compared With Chemotherapy Plus Radiation After Surgery in Treating Patients With Rectal Cancer That Can Be Surgically Removed - Full Text View

Sponsors and Collaborators:	Medical Research Council National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003422

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving radiation therapy before surgery is more effective than giving chemotherapy plus radiation therapy after surgery in treating patients with rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy given before surgery to see how well it works compared to chemotherapy and radiation therapy given after surgery in treating patients with rectal cancer that can be surgically removed.

Condition	Intervention	Phase
Colorectal Cancer	Drug: fluorouracil Drug: leucovorin calcium Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Randomised Trial Comparing Pre-Operative Radiotherapy and Selective Post-Operative Chemoradiotherapy in Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer Radiation Therapy Surgery

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result [ Designated as safety issue: No ]

Secondary Outcome Measures:

Local recurrence-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to appearance of distant metastases [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Morbidity [ Designated as safety issue: No ]
Quality of life [ Designated as safety issue: No ]
Economic implications [ Designated as safety issue: No ]

Estimated Enrollment:	1800
Study Start Date:	January 1998

Detailed Description:

OBJECTIVES:

Compare local recurrence free rates and quality of life in patients with operable rectal cancer receiving preoperative radiotherapy versus patients receiving selective postoperative chemoradiotherapy.
Determine local recurrence free survival, overall survival, time to appearance of distant metastases, disease free survival and morbidity in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by a number of factors including surgeon.

Patients are randomized to receive preoperative radiotherapy (arm I) or postoperative chemoradiotherapy (arm II).

Arm I: Patients receive radiotherapy in 5 fractions over 1 week prior to surgery. Patients undergo surgery within 7 days of the last fraction of radiotherapy.
Arm II: Patients receive chemoradiotherapy 4-12 weeks after surgery (if circumferential resection margins are histologically involved by tumor).

Radiotherapy is administered in 25 fractions over 5 weeks (5 days per week). During radiotherapy, patients either receive fluorouracil (5-FU) continuous infusion, 5-FU bolus IV and leucovorin calcium IV weekly, or a 5-day bolus schedule of 5-FU and leucovorin calcium.

Patients may then receive adjuvant chemotherapy as per local policy.

Quality of life assessments are made every 3 months for 1 year and then every 6 months for the next 2 years.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1800 patients will be accrued into this study.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum (defined as lower edge of tumor within 15 cm of anal verge)
Tumor considered potentially operable
No evidence of metastases indicated by liver ultrasound or CT scan; chest x-ray; or renal, liver, and bone profiles

PATIENT CHARACTERISTICS:

Age:

75 and under

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Cardiovascular:

No uncontrolled heart failure or angina

Other:

No other concurrent uncontrolled medical illness (e.g., infection)
No other prior or concurrent malignancy likely to interfere with the protocol treatments or comparisons

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003422

Locations

Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Saint John Regional Hospital
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 5P9
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 1C4
St. Catharines General Hospital at Niagara Health System
St. Catharines, Ontario, Canada, L2R 5K3
Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada, J4V 2H1
United Kingdom, Scotland
Ninewells Hospital and Medical School
Dundee, Scotland, United Kingdom, DD1 9SY

Sponsors and Collaborators

Medical Research Council

National Cancer Institute of Canada

Investigators

Study Chair:	R. Steele	Ninewells Hospital
Study Chair:	Jean Couture, MD	Hopital Charles Lemoyne

More Information

Additional Information:

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

Publications:

Quirke P, Steele R, Monson J, Grieve R, Khanna S, Couture J, O'Callaghan C, Myint AS, Bessell E, Thompson LC, Parmar M, Stephens RJ, Sebag-Montefiore D; MRC CR07/NCIC-CTG CO16 Trial Investigators; NCRI Colorectal Cancer Study Group. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. 2009 Mar 7;373(9666):821-8.

Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20.

Quirke P, Sebag-Montefiore D, Steele R, et al.: Local recurrence after rectal cancer resection is strongly related to the plane of surgical dissection and is further reduced by pre-operative short course radiotherapy. Preliminary results of the Medical Research Council (MRC) CR07 trial. [Abstract] J Clin Oncol 24 (Suppl 18): A-3512, 2006.

Sebag-Montefiore D, Steele R, Quirke P, et al.: Routine short course pre-op radiotherapy or selective post-op chemoradiotherapy for resectable rectal cancer? Preliminary results of the MRC CR07 randomised trial. [Abstract] J Clin Oncol 24 (Suppl 18): A-3511, 2006.

Sebag-Montefiore D: An update report on the MRC CR07 trial. [Abstract] Br J Cancer 85 (suppl 1): A-9.3, 28, 2001.

Study ID Numbers:	CDR0000066442, MRC-CR07, EU-98008, CAN-NCIC-C016, ISRCTN28785842
Study First Received:	November 1, 1999
Last Updated:	March 25, 2009
ClinicalTrials.gov Identifier:	NCT00003422 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Leucovorin
Rectal Diseases
Vitamins
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Rectal Neoplasm
Adjuvants, Immunologic

Trace Elements
Intestinal Diseases
Folinic Acid
Immunosuppressive Agents
Intestinal Neoplasms
Calcium, Dietary
Rectal Cancer
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Antineoplastic Agents
Colonic Diseases
Physiological Effects of Drugs
Leucovorin
Rectal Diseases
Neoplasms by Site
Therapeutic Uses
Vitamins

Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Growth Substances
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on July 02, 2009