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

NCT ID: NCT00002523

Last Updated: 2016-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1011 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1993-04-30
• Study Completion Date: 2016-01-31

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

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Francois Bosset, MD

Role: STUDY_CHAIR

Hopital Jean Minjoz

Locations

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Hopital Civil de Charleroi

Charleroi, , Belgium

Centre Hospitalier Universitaire de Tivoli

La Louvière, , Belgium

Clinique Sainte Elisabeth

Namur, , Belgium

Centre Paul Papin

Angers, , France

Institut Sainte Catherine

Avignon, , France

Centre Hospitalier General

Belfort, , France

CHR de Besancon - Hopital Jean Minjoz

Besançon, , France

C.H.U. de Brest

Brest, , France

Centre Hospitalier Universitaire Henri Mondor

Créteil, , France

Centre de Lutte Contre le Cancer, Georges-Francois Leclerc

Dijon, , France

CHR de Grenoble - La Tronche

Grenoble, , France

Centre Oscar Lambret

Lille, , France

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Service Cancerologie Polyclinique Clairval

Marseille, , France

CRLCC Nantes - Atlantique

Nantes-Saint Herblain, , France

Clinique De Valdegour

Nîmes, , France

Hopital Jean Bernard

Poitiers, , France

Clinique Sainte Clotilde

Sainte Clotilde, , France

Centre Paul Strauss

Strasbourg, , France

Centre Hospitalier Universitaire Bretonneau de Tours

Tours, , France

Centre Saint-Yves

Vannes, , France

Krankenhaus des Kreises Hameln-Pyrmont

Hamelin, , Germany

Rambam Medical Center

Haifa, , Israel

University Medical Center Nijmegen

Nijmegen, , Netherlands

Dr. Bernard Verbeeten Instituut

Tilburg, , Netherlands

Medical University of Gdansk

Gdansk, , Poland

Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

Hospital General Universitari Vall d'Hebron

Barcelona, , Spain

Institut Catala d'Oncologia - Hospital Duran i Reynals

Barcelona, , Spain

Hospital General Gregorio Maranon

Madrid, , Spain

Kantonsspital Basel

Basel, , Switzerland

UniversitaetsSpital

Zurich, , Switzerland

Dokuz Eylul University School of Medicine

Izmir, , Turkey (Türkiye)

Countries

Belgium; France; Germany; Israel; Netherlands; Poland; Serbia; Spain; Switzerland; Turkey (Türkiye)

References

Bonnetain F, Bosset J, Gerard J, et al.: An analysis of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer on survival in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? [Abstract] J Clin Oncol 29 (Suppl 15): A-3506, 2011.

Reference Type: BACKGROUND

den 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.

Reference Type: BACKGROUND

PMID: 19128956 (View on PubMed)

Monnien 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.

Reference Type: RESULT

PMID: 20876317 (View on PubMed)

Tiv 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.

Reference Type: RESULT

PMID: 20797891 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17906203 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16971718 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 16009958 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 12204666 (View on PubMed)

Bosset 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.

Reference Type: DERIVED

PMID: 24440473 (View on PubMed)

Other Identifiers

EORTC-22921

Identifier Type: -

Identifier Source: secondary_id

EORTC-22921

Identifier Type: -

Identifier Source: org_study_id