Colorectal CancerPhase 3NCT00296608
Radiation Therapy With or Without Chemotherapy Before Surgery in Treating Patients With Stage II or Stage III Rectal Cancer
A Phase 3 study testing fluorouracil, leucovorin calcium and conventional surgery in people with Colorectal Cancer, run by Federation Francophone de Cancerologie Digestive.
Trial summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- fluorouracil, leucovorin calcium and conventional surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 762 participants
- Where
- No sites listed yet
- Study dates
- Apr 1993to Aug 2008
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following stage criteria:
- Stage T3, N0-2, M0 disease meeting 1 of the following criteria:
- Invasive disease in entire circumference (circular tumor)
- Tumor fixed laterally or posteriorly to pelvic structures
- Tumor adherent to the prostate and/or seminal vesicles
- Tumor infiltration into the vaginal-rectal septum
- Tumor classified as uT3 by rectal endoscopy
- Stage T4, N0-2, M0 disease meeting 1 of the following criteria:
- Clinical or radiologic evidence of pelvic organ extension (vagina, prostate, seminal vesicles, or bladder)
- Tumor extension to the anal canal or sphincter
- Tumor classified as uT4 by rectal endoscopy
- Tumor accessible by digital rectal exam
- Resectable disease
- No distant metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Creatinine < 1.36 mg/dL
- Granulocyte count > 2,000/mm^3
- Platelet count > 130,000/mm^3
- No progressive ischemic cardiomyopathy
- No acute or chronic obstruction unless treated with diversion colostomy
- No chronic inflammation of the ileum and/or colon
- No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiotherapy, or surgery for this cancer
About this study
Official title: Preoperative Radiotherapy With or Without Concurrent Chemotherapy (5-Fluorouracil and Leucovorin) in T3-4 Rectal Cancers - Randomized Trial
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether radiation therapy is more effective with or without chemotherapy when given before surgery for rectal cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy given together with fluorouracil and leucovorin to see how well they work compared to giving radiation therapy alone before surgery in treating patients with stage II or stage III rectal cancer.
Read the detailed description
OBJECTIVES:
- Compare the recurrence-free and overall survival of patients with resectable stage II or III adenocarcinoma of the rectum treated with neoadjuvant radiotherapy with or without concurrent chemotherapy comprising fluorouracil and leucovorin calcium followed by surgery and adjuvant fluorouracil and leucovorin calcium.
OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, gender, location of the tumor relative to the anal margin (0-5 cm vs > 5 cm), and tumor stage (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant therapy arms.
- Arm I: Patients receive leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 5 weeks.
- Arm II: Patients undergo radiotherapy as in arm I.
- Surgery: In both arms, patients undergo surgical resection within 3-10 weeks after completing neoadjuvant therapy.
- Adjuvant therapy: Within 3-10 weeks after surgery, all patients receive adjuvant chemotherapy comprising leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for at least 5 years.
PROJECTED ACCRUAL: A total of 762 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- fluorouracil, leucovorin calcium, conventional surgery, radiation therapy
- Keywords
- 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
conventional surgeryProcedure or surgery
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy | Active comparator | RT was delivered with photons from a linear accelerator with an energy level of 8MVor above. Receives: Procedure: conventional surgery; Radiation: radiation therapy |
| Chemotherapy and radiotherapy | Experimental | The first CT cycle was administered from days 1 to 5 of the RT treatment. LV 20 mg/m2/d was delivered intravenously immediately before administration of FU. FU 350 mg/m2/d was delivered during 20 minutes in 100 mL of saline infusion, 1 hour before RT. The second cycle was administered from days 29 to 33 of the RT treatment using the same schedule. Receives: Drug: fluorouracil; Drug: leucovorin calcium; Procedure: conventional surgery; Radiation: radiation therapy |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2006 (estimated)
- Study startApr 1993
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 762 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federation Francophone de Cancerologie Digestive
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Pierre Gerard, MD, Study chair, Centre Antoine Lacassagne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00296608
- Sponsor's protocol ID
- CDR0000466625
- Other IDs
- FFCD-9203, EU-20600
- Status last verified
- May 2016
- First submitted
- 24 Feb 2006
- Last updated
- 30 May 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Bonnetain F, Bosset JF, Gerard JP, Calais G, Conroy T, Mineur L, Bouche O, Maingon P, Chapet O, Radosevic-Jelic L, Methy N, Collette L. What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? Eur J Cancer. 2012 Aug;48(12):1781-90. doi: 10.1016/j.ejca.2012.03.016. Epub 2012 Apr 14.
PubMed 22507892Methy N, Bedenne L, Conroy T, Bouche O, Chapet O, Ducreux M, Gerard JP, Bonnetain F. Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial. Ann Oncol. 2010 Mar;21(3):518-524. doi: 10.1093/annonc/mdp340. Epub 2009 Sep 16.
PubMed 19759186Methy N, Bedenne L, Gerard J, et al.: Surrogate endpoints in neoadjuvant rectal cancer trials: statistical evaluation using data from the FFCD 9203 trial. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-466, 2008.
Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629.
PubMed 17008704Gerard J, Romestaing P, Bonnetain F, et al.: Preoperative chemotherapy (CT-RT) improves local control in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-4, S2, 2005.
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preoperative Radiotherapy With or Without Concurrent Chemotherapy (5-Fluorouracil and Leucovorin) in T3-4 Rectal Cancers - Randomized Trial
- ClinicalTrials.gov ID
- NCT00296608
- Acronym / sponsor ID
- CDR0000466625
- Conditions
- Colorectal Cancer
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 762 participants (actual)
- Lead sponsor
- Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
- Study start
- Apr 1993
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 27 Feb 2006 (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 kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether radiation therapy is more effective with or without chemotherapy when given before surgery for rectal cancer.
PURPOSE: This randomized phase III trial is studying radiation therapy given together with fluorouracil and leucovorin to see how well they work compared to giving radiation therapy alone before surgery in treating patients with stage II or stage III rectal cancer.
Detailed description
OBJECTIVES:
- Compare the recurrence-free and overall survival of patients with resectable stage II or III adenocarcinoma of the rectum treated with neoadjuvant radiotherapy with or without concurrent chemotherapy comprising fluorouracil and leucovorin calcium followed by surgery and adjuvant fluorouracil and leucovorin calcium.
OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, gender, location of the tumor relative to the anal margin (0-5 cm vs > 5 cm), and tumor stage (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant therapy arms.
- Arm I: Patients receive leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 5 weeks.
- Arm II: Patients undergo radiotherapy as in arm I.
- Surgery: In both arms, patients undergo surgical resection within 3-10 weeks after completing neoadjuvant therapy.
- Adjuvant therapy: Within 3-10 weeks after surgery, all patients receive adjuvant chemotherapy comprising leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 6 months for at least 5 years.
PROJECTED ACCRUAL: A total of 762 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy | Active comparator | Procedure: conventional surgery, Radiation: radiation therapyRT was delivered with photons from a linear accelerator with an energy level of 8MVor above. |
| Chemotherapy and radiotherapy | Experimental | Drug: fluorouracil, Drug: leucovorin calcium, Procedure: conventional surgery, Radiation: radiation therapyThe first CT cycle was administered from days 1 to 5 of the RT treatment. LV 20 mg/m2/d was delivered intravenously immediately before administration of FU. FU 350 mg/m2/d was delivered during 20 minutes in 100 mL of saline infusion, 1 hour before RT. The second cycle was administered from days 29 to 33 of the RT treatment using the same schedule. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 | Chemotherapy and radiotherapy |
| leucovorin calcium | Drug | Chemotherapy and radiotherapy |
| conventional surgery | Procedure or surgery | Chemotherapy and radiotherapy, Radiotherapy |
| radiation therapy | Radiation | Chemotherapy and radiotherapy, Radiotherapy |
Primary outcome
Not reported in the source record.
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 30 May 2016.
- Background: PubMed 22507892Bonnetain F, Bosset JF, Gerard JP, Calais G, Conroy T, Mineur L, Bouche O, Maingon P, Chapet O, Radosevic-Jelic L, Methy N, Collette L. What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? Eur J Cancer. 2012 Aug;48(12):1781-90. doi: 10.1016/j.ejca.2012.03.016. Epub 2012 Apr 14.
- Results publication: PubMed 19759186Methy N, Bedenne L, Conroy T, Bouche O, Chapet O, Ducreux M, Gerard JP, Bonnetain F. Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial. Ann Oncol. 2010 Mar;21(3):518-524. doi: 10.1093/annonc/mdp340. Epub 2009 Sep 16.
- Results publicationMethy N, Bedenne L, Gerard J, et al.: Surrogate endpoints in neoadjuvant rectal cancer trials: statistical evaluation using data from the FFCD 9203 trial. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-466, 2008.
- Results publication: PubMed 17008704Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. doi: 10.1200/JCO.2006.06.7629.
- Results publicationGerard J, Romestaing P, Bonnetain F, et al.: Preoperative chemotherapy (CT-RT) improves local control in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-4, S2, 2005.
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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.
Jean-Pierre Gerard, MD study chair
Centre Antoine Lacassagne
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fluorouracil, leucovorin calcium and conventional surgery in people with Colorectal Cancer, run by Federation Francophone de Cancerologie Digestive.
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 30 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00296608, which also lists 5 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 30 May 2016.