Radiation Therapy With or Without Chemotherapy Before Surgery in Treating Patients With Stage II or Stage III Rectal Cancer - Full Text View

Sponsored by:	Fondation Francaise de Cancerologie Digestive
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00296608

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy and chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether radiation therapy is more effective with or without chemotherapy when given before surgery for rectal cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy given together with fluorouracil and leucovorin to see how well they work compared to giving radiation therapy alone before surgery in treating patients with stage II or stage III rectal cancer.

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

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Fluorouracil Calcium gluconate Liothyronine sodium Triiodothyronine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Preoperative Radiotherapy With or Without Concurrent Chemotherapy (5-Fluorouracil and Leucovorin) in T3-4 Rectal Cancers - Randomized Trial

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

Estimated Enrollment:

762

Detailed Description:

OBJECTIVES:

Compare the recurrence-free and overall survival of patients with resectable stage II or III adenocarcinoma of the rectum treated with neoadjuvant radiotherapy with or without concurrent chemotherapy comprising fluorouracil and leucovorin calcium followed by surgery and adjuvant fluorouracil and leucovorin calcium.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, gender, location of the tumor relative to the anal margin (0-5 cm vs > 5 cm), and tumor stage (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant therapy arms.
- Arm I: Patients receive leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 5 weeks.
- Arm II: Patients undergo radiotherapy as in arm I.
Surgery: In both arms, patients undergo surgical resection within 3-10 weeks after completing neoadjuvant therapy.
Adjuvant therapy: Within 3-10 weeks after surgery, all patients receive adjuvant chemotherapy comprising leucovorin calcium IV and fluorouracil IV over 15 minutes on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for at least 5 years.

PROJECTED ACCRUAL: A total of 762 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following stage criteria:
- Stage T3, N0-2, M0 disease meeting 1 of the following criteria:
  - Invasive disease in entire circumference (circular tumor)
  - Tumor fixed laterally or posteriorly to pelvic structures
  - Tumor adherent to the prostate and/or seminal vesicles
  - Tumor infiltration into the vaginal-rectal septum
  - Tumor classified as uT3 by rectal endoscopy
- Stage T4, N0-2, M0 disease meeting 1 of the following criteria:
  - Clinical or radiologic evidence of pelvic organ extension (vagina, prostate, seminal vesicles, or bladder)
  - Tumor extension to the anal canal or sphincter
  - Tumor classified as uT4 by rectal endoscopy
Tumor accessible by digital rectal exam
Resectable disease
No distant metastases

PATIENT CHARACTERISTICS:

WHO performance status 0-1
Creatinine < 1.36 mg/dL
Granulocyte count > 2,000/mm^3
Platelet count > 130,000/mm^3
No progressive ischemic cardiomyopathy
No acute or chronic obstruction unless treated with diversion colostomy
No chronic inflammation of the ileum and/or colon
No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or surgery for this cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00296608

Sponsors and Collaborators

Fondation Francaise de Cancerologie Digestive

Investigators

Study Chair:

Jean-Pierre Gerard, MD

Centre Antoine Lacassagne

More Information

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

Publications of Results:

Methy N, Bedenne L, Gerard J, et al.: Surrogate endpoints in neoadjuvant rectal cancer trials: statistical evaluation using data from the FFCD 9203 trial. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-466, 2008.

Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5.

Gerard J, Romestaing P, Bonnetain F, et al.: Preoperative chemotherapy (CT-RT) improves local control in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-4, S2, 2005.

Study ID Numbers:	CDR0000466625, FFCD-9203, EU-20600
Study First Received:	February 24, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00296608
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

Study placed in the following topic categories:

Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Leucovorin
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Rectal neoplasm
Calcium, Dietary
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on January 15, 2009