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

Colorectal Cancer Clinical Trial

Official title:

A Randomised Trial Comparing Pre-Operative Radiotherapy and Selective Post-Operative Chemoradiotherapy in Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003422
• Other study ID #: CDR0000066442
• Secondary ID: MRC-CR07EU-98008
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: December 3, 2013
• Start date: January 1998
• Est. completion date: June 2010

Study information

• Verified date: March 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1800
• Est. completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer

Intervention

Drug:
• fluorouracil

• leucovorin calcium

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	St. Catharines General Hospital at Niagara Health System	St. Catharines	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United Kingdom	Ninewells Hospital and Medical School	Dundee	Scotland

Sponsors (2)

Lead Sponsor	Collaborator
Medical Research Council	Canadian Cancer Trials Group

Countries where clinical trial is conducted

Canada,  United Kingdom, 

References & Publications (6)

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 Re

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 — View Citation

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-35

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 r — View Citation

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

Stephens RJ, Thompson LC, Quirke P, Steele R, Grieve R, Couture J, Griffiths GO, Sebag-Montefiore D. Impact of short-course preoperative radiotherapy for rectal cancer on patients' quality of life: data from the Medical Research Council CR07/National Canc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result			No
Secondary	Local recurrence-free survival			No
Secondary	Overall survival			No
Secondary	Time to appearance of distant metastases			No
Secondary	Disease-free survival			No
Secondary	Morbidity			No
Secondary	Quality of life			No
Secondary	Economic implications			No