Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00068692

Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which adjuvant combination chemotherapy regimen is more effective in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for rectal cancer.

PURPOSE: This randomized phase III trial is comparing the effectiveness of three adjuvant combination chemotherapy regimens in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for stage II or stage III rectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: FOLFOX regimen Drug: capecitabine Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Intergroup Randomized Phase III Study Of Postoperative Irinotecan, 5-Fluorouracil And Leucovorin Vs Oxaliplatin, 5-Flourouracil And Leucovorin Vs 5-Fluorouracil And Leucovorin For Patients With Stage II or III Rectal Cancer Receiving Either Preoperative Radiation And 5-Fluorouracil Or Postoperative Radiation And 5-Flourouracil

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer Surgery

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Irinotecan U 101440E Irinotecan hydrochloride Capecitabine Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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

Study Start Date:

October 2003

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Detailed Description:

OBJECTIVES:

Primary

Compare the overall survival of patients with stage II or III rectal cancer receiving preoperative (group 1) or postoperative (group 2) radiotherapy and fluorouracil when additionally treated with adjuvant irinotecan, fluorouracil, and leucovorin calcium vs oxaliplatin, fluorouracil, and leucovorin calcium vs fluorouracil and leucovorin calcium.

Secondary

Determine sphincter preservation, tolerance of treatment, and patterns of failure in patients treated with these regimens.
Determine rectal function in patients treated with postoperative pelvic radiotherapy and chemotherapy.
Correlate tumor molecular prognostic markers (chromosome 18q allelic loss and microsatellite instability) with survival of patients treated with these regimens.
Determine physician preference in regard to the radiotherapy-chemotherapy sequence in these patients.
Correlate p53 gene mutation in tumor tissue with treatment efficacy in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), chemotherapy/radiotherapy sequence (preoperative vs postoperative), and risk group (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2, N+, M0 or T3, N0, M0]). Patients are treated in 1 of 2 groups according to physician preference and then randomized to 1 of 3 treatment arms.

Group 1 (preoperative chemoradiotherapy and additional adjuvant chemotherapy):
- Preoperative chemoradiotherapy: Patients receive 1 of 3 treatment regimens, determined by the treating physician.
  - Regimen A (radiotherapy and fluorouracil): Patients undergo external beam radiotherapy once daily 5 days a week for 5 1/2 weeks (total of 28 fractions). Patients also receive concurrent fluorouracil IV continuously 7 days a week for 5 1/2 weeks.
  - Regimen B (radiotherapy, fluorouracil, and leucovorin calcium): Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent fluorouracil IV and leucovorin calcium IV continuously for 4 days on weeks 1 and 5.
  - Regimen C (radiotherapy and capecitabine)*: Patients undergo external beam radiotherapy as in regimen A. Patients also receive concurrent oral capecitabine twice daily for 5 1/2 weeks.

NOTE: *Regimen C is allowed only for patients enrolled on protocol NSABP-R-04.

Surgery: Within 21-56 days after the completion of chemoradiotherapy, patients undergo surgical resection.
Additional adjuvant chemotherapy: Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
- Arm II: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
- Arm III: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Group 2 (postoperative chemoradiotherapy and additional adjuvant chemotherapy): Within 21-56 days after complete surgical resection, patients are randomized to 1 of 3 treatment arms.
- Arm I: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I for 4 courses.
- Arm II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm II for 4 courses.
- Arm III: Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1 course.

Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A, B, or C, followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II and 2 additional courses of adjuvant chemotherapy for arm III.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 3,000 patients (1,000 per treatment arm) will be accrued for this study over 5 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- Stage II or III (T3-4, N0, M0 or any T, N1-3, M0)
No distant metastases
- No evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy
Distal border of the tumor must be or have been at or below the peritoneal reflection, defined as within 12 cm of anal verge by protoscopic examination* NOTE: *Tumor with a portion confirmed to be below the peritoneal reflection at the time of surgery is allowed regardless of the distance by endoscopy
Transmural penetration of tumor through the muscularis propria by CT scan, endorectal ultrasound, or MRI (group 1)
Tumor must be defined prospectively by the surgeon as clinically resectable or not (group 1)
Tumor may be clinically fixed or initially not completely resectable (clinical stage T4, N0-2, M0) based on the presence of at least 1 of the following criteria (group 1):
- Tumor adherent to the pelvic sidewall or sacrum on rectal examination
- Hydronephrosis on CT scan or intravenous pyelogram OR ureteric or bladder invasion by cystoscopy and cytology or biopsy OR invasion into prostate
- Vaginal or uterine involvement

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST no greater than 3 times ULN

Renal

Creatinine no greater than 1.5 times ULN

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other prior or concurrent malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other treated non-pelvic cancer from which the patient has been disease-free for more than 5 years
No active inflammatory bowel disease
No other serious medical illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy to the pelvis
No concurrent intraoperative radiotherapy and/or brachytherapy

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068692

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Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Al B. Benson, MD, FACP	Robert H. Lurie Cancer Center
Investigator:	Bruce J. Giantonio, MD	Presbyterian Medical Center
Investigator:	Neal J. Meropol, MD	Fox Chase Cancer Center

More Information

Additional Information:

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

Publications:

Benson AB, Catalano P, Meropol NJ, et al.: ECOG E3201: intergroup randomized phase III study of postoperative irinotecan, 5- fluorouracil (FU), leucovorin (LV) (FOLFIRI) vs oxaliplatin, FU/LV (FOLFOX) vs FU/LV for patients (pts) with stage II/ III rectal cancer receiving either pre or postoperative radiation (RT)/ FU. [Abstract] J Clin Oncol 24 (Suppl 18): A-3526, 152s, 2006.

Study ID Numbers:	CDR0000327815, ECOG-E3201
Study First Received:	September 10, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00068692 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Irinotecan
Physiological Effects of Drugs
Leucovorin
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins

Therapeutic Uses
Micronutrients
Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Adjuvants, Immunologic
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin
Pharmacologic Actions
Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on November 27, 2009