History of Changes for Study: NCT00002523

Radiation Therapy, Surgery, and Chemotherapy in Treating Patients With Rectal Cancer That Can Be Surgically Removed

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Study Record Versions

Version	Submitted Date	Changes
1	June 23, 2005	None (earliest Version on record)
2	November 29, 2006	References, Eligibility and Study Status
3	January 11, 2007	Study Status
4	February 8, 2007	References, Contacts/Locations, Conditions, Study Status, Eligibility, Study Design and Study Identification
5	October 13, 2007	References and Study Status
6	October 25, 2007	Arms and Interventions and Study Status
7	November 16, 2007	Study Status
8	November 17, 2007	Study Status
9	December 15, 2007	Study Status
10	December 25, 2007	Study Status
11	January 5, 2008	Study Status
12	January 12, 2008	Study Status
13	January 20, 2008	Study Status
14	March 1, 2008	Study Status
15	March 8, 2008	Study Status
16	May 23, 2008	Arms and Interventions and Study Status
17	July 23, 2008	Contacts/Locations and Study Status
18	January 13, 2009	References and Study Status
19	February 6, 2009	Arms and Interventions and Study Status
20	September 1, 2010	References and Study Status
21	October 8, 2010	References and Study Status
22	July 20, 2011	References and Study Status
23	September 1, 2016	Recruitment Status, Study Status, Study Identification, Study Design and Sponsor/Collaborators

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CDR0000078308
Brief Title:	Radiation Therapy, Surgery, and Chemotherapy in Treating Patients With Rectal Cancer That Can Be Surgically Removed
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
Secondary IDs:	EORTC-22921

Study Status


Record Verification:	September 2002
Overall Status:	Active, not recruiting
Study Start:	April 1993
Primary Completion:
Study Completion:

First Submitted:	November 1, 1999
First Submitted that Met QC Criteria:	January 26, 2003
First Posted:	January 27, 2003 [Estimate]

Last Update Submitted that Met QC Criteria:	November 17, 2007
Last Update Posted:	November 19, 2007 [Estimate]

Sponsor/Collaborators


Sponsor:	European Organisation for Research and Treatment of Cancer - EORTC
Responsible Party:
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:

Study Description

Brief 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.

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.

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


Conditions:	Colorectal Cancer
Keywords:	stage II rectal cancer stage III rectal cancer adenocarcinoma of the rectum

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:
Number of Arms:
Masking:	(masked roles unspecified)
Allocation:	Randomized
Enrollment:

Arms and Interventions


Intervention Details:
	Drug: fluorouracil
	Drug: leucovorin calcium
	Procedure: chemotherapy
	Procedure: conventional surgery
	Procedure: drug modulation therapy
	Procedure: radiation therapy
	Procedure: radiosensitization

Eligibility


Minimum Age:
Maximum Age:	80 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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

Contacts/Locations


Study Officials:	Jean-Francois Bosset, MD Study Chair Hopital Jean Minjoz
Locations:	Belgium
	Institut Jules Bordet Brussels, Belgium, 1000
	Hopital Universitaire Erasme Brussels, Belgium, 1070
	Hopital Civil de Charleroi Charleroi, Belgium, 6000
	Centre Hospitalier Universitaire de Tivoli La Louviere, Belgium, 7100
	Clinique Sainte Elisabeth Namur, Belgium, 5000
	Former Serbia and Montenegro
	Institute of Oncology and Radiology of Serbia Belgrade, Former Serbia and Montenegro, 11000
	France
	Centre Paul Papin Angers, France, 49036
	Institut Sainte Catherine Avignon, France, 84082
	Centre Hospitalier General Belfort, France, 90000
	CHR de Besancon - Hopital Jean Minjoz Besancon, France, 25030
	C.H.U. de Brest Brest, France, 29200
	Centre Hospitalier Universitaire Henri Mondor Creteil, France, 94010
	Centre de Lutte Contre le Cancer, Georges-Francois Leclerc Dijon, France, 21079
	CHR de Grenoble - La Tronche Grenoble, France, 38043
	Centre Oscar Lambret Lille, France, 59020
	Centre Hospital Regional Universitaire de Limoges Limoges, France, 87042
	Service Cancerologie Polyclinique Clairval Marseille, France, 13009
	CRLCC Nantes - Atlantique Nantes-Saint Herblain, France, 44805
	Clinique De Valdegour Nimes, France, 30900
	Hopital Jean Bernard Poitiers, France, 86021
	Clinique Sainte Clotilde Sainte Clotilde, France, 97492
	Centre Paul Strauss Strasbourg, France, 67085
	Centre Hospitalier Universitaire Bretonneau de Tours Tours, France, 37044
	Centre Saint-Yves Vannes, France, 56001
	Germany
	Krankenhaus des Kreises Hameln-Pyrmont Hameln, Germany, 31785
	Israel
	Rambam Medical Center Haifa, Israel, 31096
	Netherlands
	University Medical Center Nijmegen Nijmegen, Netherlands, NL-6500 HB
	Dr. Bernard Verbeeten Instituut Tilburg, Netherlands, 5042 SB
	Poland
	Medical University of Gdansk Gdansk, Poland, 80-211
	Spain
	Hospital General Universitari Vall d'Hebron Barcelona, Spain, 08035
	Institut Catala d'Oncologia - Hospital Duran i Reynals Barcelona, Spain, 08907
	Hospital General Gregorio Maranon Madrid, Spain, 28007
	Switzerland
	Kantonsspital Basel Basel, Switzerland, CH-4000
	UniversitaetsSpital Zurich, Switzerland, CH-8091
	Turkey
	Dokuz Eylul University School of Medicine Izmir, Turkey, 35340

IPDSharing


Plan to Share IPD:

References


Citations:	[Study Results] Collette 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 17906203
	[Study Results] Bosset 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. Erratum In: N Engl J Med. 2007 Aug 16;357(7):728. PubMed 16971718
	[Study Results] Bosset 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.
	[Study Results] 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.
	[Study Results] 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 16009958
	[Study Results] Bosset 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.
	[Study Results] 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.
	[Study Results] 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 12204666
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