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

Sponsor:	European Organization for Research and Treatment of Cancer - EORTC
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002523

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: fluorouracil Drug: leucovorin calcium Procedure: conventional surgery Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

April 1993

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.

Eligibility

Ages Eligible for Study:	up to 80 Years
Genders Eligible for Study:	Both
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 and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002523

Show 35 Study Locations

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer - EORTC

Investigators

Study Chair:

Jean-Francois Bosset, MD

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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 Aug 24; [Epub ahead of print]

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.

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.

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.

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. Epub 2005 Jul 11.

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.

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 V, Bosset J, van Tienhoven G, Davis B, Pierart M, Poortmans P. 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.

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 Jan 5; [Epub ahead of print]

ClinicalTrials.gov Identifier:	NCT00002523 History of Changes
Other Study ID Numbers:	CDR0000078308, EORTC-22921
Study First Received:	November 1, 1999
Last Updated:	July 20, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II rectal cancer
stage III rectal cancer
adenocarcinoma of the rectum

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Leucovorin
Levoleucovorin

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on February 12, 2012