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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002523
• Other study ID #: EORTC-22921
• Secondary ID: EORTC-22921
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 1, 2016
• Start date: April 1993
• Est. completion date: January 2016

Study information

• Verified date: September 2016
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1011
• Est. completion date: January 2016
• Est. primary completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

Drug:
• fluorouracil

• leucovorin calcium

Procedure:
• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Hopital Civil de Charleroi	Charleroi
Belgium	Centre Hospitalier Universitaire de Tivoli	La Louviere
Belgium	Clinique Sainte Elisabeth	Namur
France	Centre Paul Papin	Angers
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier General	Belfort
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	C.H.U. de Brest	Brest
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
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	Nimes
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
Germany	Krankenhaus des Kreises Hameln-Pyrmont	Hameln
Israel	Rambam Medical Center	Haifa
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Dr. Bernard Verbeeten Instituut	Tilburg
Poland	Medical University of Gdansk	Gdansk
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Spain	Hospital General Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala d'Oncologia - Hospital Duran i Reynals	Barcelona
Spain	Hospital General Gregorio Maranon	Madrid
Switzerland	Kantonsspital Basel	Basel
Switzerland	UniversitaetsSpital	Zurich
Turkey	Dokuz Eylul University School of Medicine	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Israel,  Netherlands,  Poland,  Serbia,  Spain,  Switzerland,  Turkey, 

References & Publications (12)

Bonnetain F, Bosset JF, Gerard JP, Calais G, Conroy T, Mineur L, Bouché 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. — View Citation

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 C

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 On

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 O

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. 2 — View Citation

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. E — View Citation

Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Piérart M, Calais G; European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Patients with curative resection of cT3-4 rectal cancer after pr — View Citation

den Dulk M, Putter H, Collette L, Marijnen CA, Folkesson J, Bosset JF, Rödel C, Bujko K, Påhlman L, van de Velde CJ. 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):1175-83. doi: 10.1016/j.ejca.2008.11.039. Epub 2009 Jan 6. — View Citation

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 chem — View Citation

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):8 — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references