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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Radiation: radiation therapy; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Procedure: conventional surgery

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1800
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result

Secondary Outcome Measures

Outcome Measure
Overall survival
Quality of life
Disease-free survival
Local recurrence-free survival
Morbidity
Time to appearance of distant metastases
Economic implications

Collaborators and Investigators

• Sponsor: Medical Research Council
• Collaborators: NCIC Clinical Trials Group
• Investigators: Study Chair: R. Steele, Ninewells Hospital; Study Chair: Jean Couture, MD, Hopital Charles LeMoyne

Publications and helpful links

General Publications

• 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. doi: 10.1016/S0140-6736(09)60484-0.
• 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 Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol. 2010 Sep 20;28(27):4233-9. doi: 10.1200/JCO.2009.26.5264. Epub 2010 Jun 28.
• 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. doi: 10.1016/S0140-6736(09)60485-2.
• 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 record dates

Study Major Dates

• Study Start: January 1, 1998
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 4, 2013
• Last Update Submitted That Met QC Criteria: December 3, 2013
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage II rectal cancer; stage III rectal cancer; stage I rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: CDR0000066442; MRC-CR07; EU-98008; CAN-NCIC-C016; ISRCTN28785842