Colorectal CancerPhase 3NCT00003422
Radiation Therapy Before Surgery Compared With Chemotherapy Plus Radiation After Surgery in Treating Patients With Rectal Cancer That Can Be Surgically Removed
A Phase 3 study testing fluorouracil, leucovorin calcium and adjuvant therapy in people with Colorectal Cancer, run by Medical Research Council at 9 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- fluorouracil, leucovorin calcium and adjuvant therapy
- Type of treatment
- Surgery or procedure
- How many people
- 1,800 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Jan 1998to Jun 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
Canada8 sites
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, T2N 4N2
Hopital Charles Lemoyne
Greenfield Park, Quebec, J4V 2H1
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, K7L 5P9
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, K1H 1C4
Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2
St. Catharines General Hospital at Niagara Health System
St. Catharines, Ontario, L2R 5K3
Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
United Kingdom1 site
Ninewells Hospital and Medical School
Dundee, Scotland, DD1 9SY
About this study
Official title: 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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- fluorouracil, leucovorin calcium, adjuvant therapy, conventional surgery, neoadjuvant therapy
- Keywords
- stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluorouracilDrug
adjuvant therapyProcedure or surgery
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result
Secondary outcomes (7)
Local recurrence-free survival
Overall survival
Time to appearance of distant metastases
Disease-free survival
Morbidity
Quality of life
Economic implications
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJan 1998
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Enrolment
- 1,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical Research Council
- Sponsor type
- Other government
- Collaborators
- NCIC Clinical Trials Group
- Investigators
- R. Steele, Study chair, Ninewells HospitalJean Couture, MD, Study chair, Hopital Charles Lemoyne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003422
- Sponsor's protocol ID
- CDR0000066442
- Other IDs
- MRC-CR07, EU-98008, CAN-NCIC-C016, ISRCTN28785842
- Status last verified
- Mar 2007
- First submitted
- 1 Nov 1999
- Last updated
- 4 Dec 2013
- Results posted
- No
Publications
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.
PubMed 20585099Quirke 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.
PubMed 19269520Sebag-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.
PubMed 19269519Quirke 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 at a glance
From the registry record, last updated by the sponsor on 4 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Trial Comparing Pre-Operative Radiotherapy and Selective Post-Operative Chemoradiotherapy in Rectal Cancer
- ClinicalTrials.gov ID
- NCT00003422
- Acronym / sponsor ID
- CDR0000066442
- Conditions
- Colorectal Cancer
- Keywords
- stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,800 participants (estimated)
- Lead sponsor
- Medical Research CouncilOther government
- Collaborators
- NCIC Clinical Trials Group
- Study start
- Jan 1998
- Study completion
- Jun 2010 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluorouracil | Drug | – |
| leucovorin calcium | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result
7 secondary outcomes
Local recurrence-free survival
Overall survival
Time to appearance of distant metastases
Disease-free survival
Morbidity
Quality of life
Economic implications
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2013.
- Results publication: PubMed 20585099Stephens 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.
- Results publication: PubMed 19269520Quirke 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.
- Results publication: PubMed 19269519Sebag-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.
- Results publicationQuirke 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.
- Results publicationSebag-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.
- Results publicationSebag-Montefiore D: An update report on the MRC CR07 trial. [Abstract] Br J Cancer 85 (suppl 1): A-9.3, 28, 2001.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R. Steele study chair
Ninewells Hospital
Jean Couture, MD study chair
Hopital Charles Lemoyne
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fluorouracil, leucovorin calcium and adjuvant therapy in people with Colorectal Cancer, run by Medical Research Council at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local recurrence by biopsy, imaging, or imaging and carcinoembryonic antigen result. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00003422, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2013.