Colorectal CancerPhase 3NCT00002523
Radiation Therapy, Surgery, and Chemotherapy in Treating Patients With Rectal Cancer That Can Be Surgically Removed
A Phase 3 study testing fluorouracil, leucovorin calcium and conventional surgery in people with Colorectal Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 35 sites in 10 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, giving the drugs in different ways, and combining radiation therapy and surgery with chemotherapy may kill more tumor cells. Read more about this study
- Who is it for?
- Ages Up to 80 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- fluorouracil, leucovorin calcium and conventional surgery
- Type of treatment
- Surgery or procedure
- How many people
- 1,011 participants
- Where
- 35 sitesin 10 countries
- Study dates
- Apr 1993to Jan 2016
- Phase
- Phase 3
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 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed resectable adenocarcinoma of the rectum
- Any grade
- Tumor macroscopically within 15 cm of anal margin on rigid rectoscopy
- Tumor tethered or partially fixed on digital rectal exam and/or T3-4 on rectal ultrasound
- No acute or subacute bowel obstruction without colostomy diversion
- No chronic inflammatory disease of the ileum and/or colon
- No primary adenocarcinoma of the anal canal
- No distant metastasis
PATIENT CHARACTERISTICS:
Age:
- 80 and under
Performance status:
- WHO 0-1
Life expectancy:
- Not specified
Hematopoietic:
- Granulocyte count greater than 2,000/mm^3
- Platelet count greater than 130,000/mm^3
Hepatic:
- Not specified
Renal:
- Creatinine less than 1.36 mg/dL
Cardiovascular:
- No angina pectoris
Other:
- No other prior malignancy except basal cell skin cancer or carcinoma in situ of the uterine cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior biologic therapy for adenocarcinoma of the rectum
Chemotherapy
- No prior chemotherapy for adenocarcinoma of the rectum
Endocrine therapy
- No prior endocrine therapy for adenocarcinoma of the rectum
Radiotherapy
- No prior radiotherapy for adenocarcinoma of the rectum
Surgery
- No prior surgery for adenocarcinoma of the rectum
Trial locations and contacts
35 sites in 10 countries.
35 sites in 10 countries
France18 sites
Centre Paul Papin
Angers, 49036
Institut Sainte Catherine
Avignon, 84082
Centre Hospitalier General
Belfort, 90000
CHR de Besancon - Hopital Jean Minjoz
Besançon, 25030
C.H.U. de Brest
Brest, 29200
Centre Hospitalier Universitaire Henri Mondor
Créteil, 94010
Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
Dijon, 21079
CHR de Grenoble - La Tronche
Grenoble, 38043
Centre Oscar Lambret
Lille, 59020
Centre Hospital Regional Universitaire de Limoges
Limoges, 87042
Service Cancerologie Polyclinique Clairval
Marseille, 13009
CRLCC Nantes - Atlantique
Nantes-Saint Herblain, 44805
Clinique De Valdegour
Nîmes, 30900
Hopital Jean Bernard
Poitiers, 86021
Clinique Sainte Clotilde
Sainte Clotilde, 97492
Centre Paul Strauss
Strasbourg, 67085
Centre Hospitalier Universitaire Bretonneau de Tours
Tours, 37044
Centre Saint-Yves
Vannes, 56001
Belgium5 sites
Institut Jules Bordet
Brussels, 1000
Hopital Universitaire Erasme
Brussels, 1070
Hopital Civil de Charleroi
Charleroi, 6000
Centre Hospitalier Universitaire de Tivoli
La Louvière, 7100
Clinique Sainte Elisabeth
Namur, 5000
Spain3 sites
Hospital General Universitari Vall d'Hebron
Barcelona, 08035
Institut Catala d'Oncologia - Hospital Duran i Reynals
Barcelona, 08907
Hospital General Gregorio Maranon
Madrid, 28007
Netherlands2 sites
University Medical Center Nijmegen
Nijmegen, NL-6500 HB
Dr. Bernard Verbeeten Instituut
Tilburg, 5042 SB
Switzerland2 sites
Kantonsspital Basel
Basel, CH-4000
UniversitaetsSpital
Zurich, CH-8091
Turkey (Türkiye)1 site
Dokuz Eylul University School of Medicine
Izmir, 35340
About this study
Official title: FOUR ARMS PHASE III CLINICAL TRIAL FOR T3-T4 RESECTABLE RECTAL CANCER COMPARING PRE-OPERATIVE PELVIC IRRADIATION TO PRE-OPERATIVE IRRADIATION COMBINED WITH FLUOROURACIL AND LEUCOVORIN WITH OR WITHOUT POST-OPERATIVE ADJUVANT CHEMOTHERAPY
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, giving the drugs in different ways, and combining radiation therapy and surgery with chemotherapy may kill more tumor cells.
PURPOSE: Randomized phase III trial to compare radiation therapy alone before surgery with radiation therapy plus fluorouracil and leucovorin before surgery, with and without fluorouracil and leucovorin after surgery in patients with rectal cancer that can be surgically removed.
Read the detailed description
OBJECTIVES:
- Compare the disease-free and overall survival in patients with resectable adenocarcinoma of the rectum treated with preoperative radiotherapy with or without preoperative fluorouracil (5-FU) combined with leucovorin calcium (CF) and/or postoperative 5-FU/CF.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, sex, tumor location (0-5 vs 6-10 vs 11-15 cm from anal margin), and stage (T3 vs T4). Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients undergo involved-field radiotherapy 5 days a week for 5 weeks followed 3-10 weeks later by abdominoperineal resection or anal-sparing resection according to local practice in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo radiotherapy as in arm I beginning on day 1 and leucovorin calcium (CF) IV followed by fluorouracil (5-FU) IV (1 hour before radiotherapy) on days 1-5 and 29-33, followed 3-10 weeks later by resection as in arm I in the absence of disease progression or unacceptable toxicity.
- Arm III: Patients undergo radiotherapy followed 3-10 weeks later by resection as in arm I. Within 3-10 weeks after resection, patients receive CF followed by 5-FU on days 1-5. Chemotherapy continues every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm IV: Patients undergo preoperative radiotherapy with concurrent chemotherapy followed by resection as in arm II and postoperative chemotherapy as in arm III.
Patients are followed every 6 months.
PROJECTED ACCRUAL: A total of 992 patients will be accrued for this study within 4 years.
- 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
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 startApr 1993
- Primary completionMar 2003
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- 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
- 1,011 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jean-Francois Bosset, MD, Study chair, Hopital Jean Minjoz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002523
- Sponsor's protocol ID
- EORTC-22921
- Other IDs
- EORTC-22921
- Status last verified
- Sep 2016
- First submitted
- 1 Nov 1999
- Last updated
- 2 Sep 2016
- Results posted
- 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 22507892den Dulk M, Putter H, Collette L, Marijnen CAM, Folkesson J, Bosset JF, Rodel C, Bujko K, Pahlman L, van de Velde CJH. The abdominoperineal resection itself is associated with an adverse outcome: the European experience based on a pooled analysis of five European randomised clinical trials on rectal cancer. Eur J Cancer. 2009 May;45(7):1175-1183. doi: 10.1016/j.ejca.2008.11.039. Epub 2009 Jan 6.
PubMed 19128956Monnien F, Zaki H, Borg C, Mougin C, Bosset JF, Mercier M, Arbez-Gindre F, Kantelip B. Prognostic value of phosphorylated STAT3 in advanced rectal cancer: a study from 104 French patients included in the EORTC 22921 trial. J Clin Pathol. 2010 Oct;63(10):873-8. doi: 10.1136/jcp.2010.076414.
PubMed 20876317Tiv M, Puyraveau M, Mineur L, Calais G, Maingon P, Bardet E, Mercier M, Bosset JF. Long-term quality of life in patients with rectal cancer treated with preoperative (chemo)-radiotherapy within a randomized trial. Cancer Radiother. 2010 Oct;14(6-7):530-4. doi: 10.1016/j.canrad.2010.06.017. Epub 2010 Aug 24.
PubMed 20797891Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Pierart M, Calais G; European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007 Oct 1;25(28):4379-86. doi: 10.1200/JCO.2007.11.9685.
PubMed 17906203Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. doi: 10.1056/NEJMoa060829.
PubMed 16971718Bosset J, Calais G, Mineur L, et al.: Preoperative radiotherapy in rectal cancer: role and place of fluorouracil-based chemotherapy. Final results of the EORTC 22921 phase III trial. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-255, 2005.
Bosset JF, Calais G, Mineur L, et al.: Preoperative radiation (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-3505, 247s, 2005.
Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Briffaux A, Collette L. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results--EORTC 22921. J Clin Oncol. 2005 Aug 20;23(24):5620-7. doi: 10.1200/JCO.2005.02.113. Epub 2005 Jul 11.
PubMed 16009958Bosset JF, Calais G, Mineur L, et al.: Does the addition of chemotherapy (CT) to preoperative radiotherapy (preopRT) increase the pathological response in patients with resected rectal cancer: report of the 22921 EORTC phase III trial. [Abstract] J Clin Oncol 22 (Suppl 14): A-3504, 246, 2004.
Bosset JF, Calais G, Daban A, et al.: Does the addition of chemotherapy to preoperative radiation increase acute toxicity in patients with rectal cancer: report of 22921 EORTC phase III trial . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1179, 2003.
Kouloulias VE, Bosset JF, van Tienhoven G, Davis BJ, Pierart M, Poortmans P; EORTC Radiotherapy Group. European Organization for Research and Treatment of Cancer. Quality assurance in the EORTC 22921 trial on preoperative radiotherapy with or without chemotherapy for resectable rectal cancer: evaluation of the individual case review procedure. Eur J Cancer. 2002 Sep;38(14):1849-56. doi: 10.1016/s0959-8049(02)00174-0.
PubMed 12204666Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavere P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. doi: 10.1016/S1470-2045(13)70599-0. Epub 2014 Jan 17.
PubMed 24440473