Fluorouracil, Gemcitabine, and Radiation Therapy in Treating Patients With Cancer of the Pancreas - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group Southwest Oncology Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003216

Purpose

RATIONALE: Drugs used in chemotherapy 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. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known which treatment regimen is most effective for pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and gemcitabine plus radiation therapy in treating patients with cancer of the pancreas who have undergone surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: fluorouracil Drug: gemcitabine hydrochloride Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Study of Pre and Post Chemoradiation 5-FU vs. Pre and Post Chemoradiation Gemcitabine for Postoperative Adjuvant Treatment of Resected Pancreatic Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Fluorouracil Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

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

Estimated Enrollment:	518
Study Start Date:	July 1998
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Compare the overall and disease-free survival of patients with resected adenocarcinoma of the pancreas treated with adjuvant fluorouracil-based chemoradiotherapy preceded and followed by fluorouracil vs gemcitabine.
Compare the local-regional and distant disease control in patients treated with these regimens.
Compare the acute and late toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal involvement (yes vs no), tumor diameter (less than 3 cm vs 3 cm or greater), and surgical margins (negative vs positive vs unknown). Patients are randomized to one of two treatment arms.

Arm I: Beginning 3-8 weeks after definitive surgical resection, patients receive fluorouracil IV continuously for 3 weeks. Beginning 1-2 weeks later, patients receive fluorouracil IV continuously concurrently with radiotherapy 5 days a week for 5.5 weeks. Beginning 3-5 weeks after completion of chemoradiotherapy, patients receive fluorouracil IV continuously for 4 weeks every 6 weeks for 2 courses.
Arm II: Beginning 3-8 weeks after definitive surgical resection, patients receive gemcitabine IV once weekly for 3 weeks. Beginning 1-2 weeks later, patients receive chemoradiotherapy as in arm I. Beginning 3-5 weeks after completion of chemoradiotherapy, patients receive gemcitabine IV once weekly for 3 weeks every 4 weeks for 3 courses.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 518 patients will be accrued for this study within 8.6 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 pancreas
- Stage T1-4, N0-1 (stage I-IVA)
- No M1 or NX staging
- Primary tumor of the pancreas (pancreatic head, neck, uncinate process, or body/tail) and maximum diameter/dimension and tumor status at surgical margin known
Prior potentially curative gross resection within 3-8 weeks before study
No non-adenocarcinomas, adenosquamous carcinomas, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct carcinoma, or ampullary carcinoma
No recurrent disease
Post-resection CA-19-9 level required

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT no greater than 5 times ULN

Renal:

Creatinine no greater than 1.5 times ULN

Other:

No significant nausea or vomiting
No prior malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix
Able to maintain adequate nutrition (at least 1,500 calories/day)
- Feeding tube allowed
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy

Surgery:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003216

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Locations

United States, Alabama
MBCCOP - Gulf Coast
Mobile, Alabama, United States, 36688
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, United States, 85723
Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
Phoenix, Arizona, United States, 85012
CCOP - Greater Phoenix
Phoenix, Arizona, United States, 85006-2726
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Veterans Affairs Medical Center - Little Rock (McClellan)
Little Rock, Arkansas, United States, 72205
United States, California
CCOP - Bay Area Tumor Institute
Oakland, California, United States, 94609-3305
CCOP - Santa Rosa Memorial Hospital
Santa Rosa, California, United States, 95403
David Grant Medical Center
Travis Air Force Base, California, United States, 94535
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
University of California Davis Medical Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033-0804
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
Veterans Affairs Medical Center - West Los Angeles
Los Angeles, California, United States, 90073
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Colorado
University of Colorado Cancer Center
Denver, Colorado, United States, 80010
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
United States, District of Columbia
MBCCOP - Howard University Cancer Center
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342-1701
Dwight David Eisenhower Army Medical Center
Fort Gordon, Georgia, United States, 30905-5650
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 96813-2424
Tripler Army Medical Center
Honolulu, Hawaii, United States, 96859-5000
United States, Illinois
CCOP - Central Illinois
Decatur, Illinois, United States, 62526
Loyola University Medical Center
Maywood, Illinois, United States, 60153-5500
MBCCOP - University of Illinois at Chicago
Chicago, Illinois, United States, 60612-7323
Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
Hines, Illinois, United States, 60141
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7353
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
United States, Kentucky
Albert B. Chandler Medical Center, University of Kentucky
Lexington, Kentucky, United States, 40536-0084
Veterans Affairs Medical Center - Lexington
Lexington, Kentucky, United States, 40502-2236
United States, Louisiana
Louisiana State University Health Sciences Center - Shreveport
Shreveport, Louisiana, United States, 71130-3932
MBCCOP - LSU Medical Center
New Orleans, Louisiana, United States, 70112
Tulane University School of Medicine
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center - New Orleans
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center - Shreveport
Shreveport, Louisiana, United States, 71130
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Veterans Affairs Medical Center - Boston (Jamaica Plain)
Jamaica Plain, Massachusetts, United States, 02130
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
CCOP - Ann Arbor Regional
Ann Arbor, Michigan, United States, 48106
Veterans Affairs Medical Center - Detroit
Detroit, Michigan, United States, 48201-1932
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Providence Hospital - Southfield
Southfield, Michigan, United States, 48075-9975
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0912
Veterans Affairs Medical Center - Ann Arbor
Ann Arbor, Michigan, United States, 48105
CCOP - Beaumont
Royal Oak, Michigan, United States, 48073-6769
United States, Minnesota
CCOP - Duluth
Duluth, Minnesota, United States, 55805
United States, Mississippi
Keesler Medical Center - Keesler AFB
Keesler AFB, Mississippi, United States, 39534-2576
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
Veterans Affairs Medical Center - Biloxi
Biloxi, Mississippi, United States, 39531-2410
Veterans Affairs Medical Center - Jackson
Jackson, Mississippi, United States, 39216
United States, Missouri
CCOP - Cancer Research for the Ozarks
Springfield, Missouri, United States, 65807
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
St. Louis University Health Sciences Center
Saint Louis, Missouri, United States, 63110
Veterans Affairs Medical Center - Kansas City
Kansas City, Missouri, United States, 64128
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
Veterans Affairs Medical Center - Albuquerque
Albuquerque, New Mexico, United States, 87108-5138
United States, New York
Herbert Irving Comprehensive Cancer Center
New York, New York, United States, 10032
St. Vincents Comprehensive Cancer Center
New York, New York, United States, 10011
University of Rochester Medical Center
Rochester, New York, United States, 14642
Veterans Affairs Medical Center - Albany
Albany, New York, United States, 12208
Western New York Urology Associates
Buffalo, New York, United States, 14220
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Winston-Salem, North Carolina, United States, 27104-4241
United States, Ohio
Arthur G. James Cancer Hospital - Ohio State University
Columbus, Ohio, United States, 43210-1240
Barrett Cancer Center
Cincinnati, Ohio, United States, 45267-0501
CCOP - Columbus
Columbus, Ohio, United States, 43206
CCOP - Dayton
Kettering, Ohio, United States, 45429
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-9001
Veterans Affairs Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45220-2288
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Veterans Affairs Medical Center - Oklahoma City
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
CCOP - Columbia River Program
Portland, Oregon, United States, 97225
Oregon Cancer Institute
Portland, Oregon, United States, 97239
Veterans Affairs Medical Center - Portland
Portland, Oregon, United States, 97207
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425-0721
CCOP - Upstate Carolina
Spartanburg, South Carolina, United States, 29303
CCOP - Greenville
Greenville, South Carolina, United States, 29615
Veterans Affairs Medical Center - Charleston
Charleston, South Carolina, United States, 29401-5799
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234-6200
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7845
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4095
Texas Tech University Health Science Center
Lubbock, Texas, United States, 79415
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0565
Veterans Affairs Medical Center - Houston
Houston, Texas, United States, 77030
Veterans Affairs Medical Center - San Antonio (Murphy)
San Antonio, Texas, United States, 78284
Veterans Affairs Medical Center - Temple
Temple, Texas, United States, 76504
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112-5550
Veterans Affairs Medical Center - Salt Lake City
Salt Lake City, Utah, United States, 84148
United States, Virginia
Eastern Virginia Medical School
Norfolk, Virginia, United States, 23510-1115
United States, Washington
CCOP - Northwest
Tacoma, Washington, United States, 98405-0986
CCOP - Virginia Mason Research Center
Seattle, Washington, United States, 98101
Madigan Army Medical Center
Tacoma, Washington, United States, 98431-5000
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Veterans Affairs Medical Center - Seattle
Seattle, Washington, United States, 98108
Canada, British Columbia
British Columbia Cancer Agency
Vancouver, British Columbia, Canada, V5Z 4E6

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Southwest Oncology Group

Investigators

Study Chair:	William F. Regine, MD	Lucille P. Markey Cancer Center at University of Kentucky
Study Chair:	Al B. Benson, MD, FACP	Robert H. Lurie Cancer Center
Study Chair:	John S. MacDonald, MD	St. Vincent's Comprehensive Cancer Center - Manhattan

More Information

Additional Information:

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

Publications:

Farrell J, Bae K, Guha C, et al.: Correlation of cytidine deaminase single nucleotide polymorphism and toxicity from gemcitabine in patients with pancreatic cancer from RTOG 9704. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-115, 2009.

Farrell JJ, Elsaleh H, Garcia M, Lai R, Ammar A, Regine WF, Abrams R, Benson AB, Macdonald J, Cass CE, Dicker AP, Mackey JR. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology. 2009 Jan;136(1):187-95. Epub 2008 Oct 7.

Piperdi B, Ng S, Piperdi M, et al.: Single institutional experience with oral capecitabine (Cap) in adjuvant therapy for pancreatic cancer: Gemcitabine (G) followed by Cap/RT followed by G. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-229, 2009.

Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, Konski A, Benson AB 3rd, Macdonald J, Willett CG. Postresection CA 19-9 Predicts Overall Survival in Patients With Pancreatic Cancer Treated With Adjuvant Chemoradiation: A Prospective Validation by RTOG 9704. J Clin Oncol. 2008 Nov 24; [Epub ahead of print]

Regine WF, Winter KA, Abrams RA, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Kudrimoti MR, Fromm ML, Haddock MG, Schaefer P, Willett CG, Rich TA. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008 Mar 5;299(9):1019-26.

Abrams RA, Winter KA, Regine WF, et al.: Correlation of RTOG 9704 (adjuvant therapy (rx) of pancreatic adenocarcinoma (pan ca)) radiation therapy quality assurance scores (RTQASc) with survival (S). [Abstract] J Clin Oncol 25 (Suppl 18): A-4523, 2007.

Berger AC, Winter K, Hoffman J, et al.: Post-resection CA 19-9 predicts overall survival (OS) in patients treated with adjuvant chemoradiation: a secondary endpoint of RTOG 9704. [Abstract] J Clin Oncol 25 (Suppl 18): A-4522, 2007.

Regine WF, Garcia M, Berger AC, et al.: Post-resectional CA 19-9 values >90 are associated with significantly worse survival in patients with pancreatic carcinoma treated with adjuvant therapy on RTOG 9704: implications for current and future trials. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-137, S78, 2007.

Abrams RA, Winter KA, Regine WF, et al.: RTOG 9704: radiotherapy quality assurance (QA) review and survival. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-39, S22, 2006.

Regine WF, Winter KA, Abrams R, et al.: A phase III intergroup trial (RTOG 97-04) of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-42, S23-4, 2006.

Regine WF, Winter KW, Abrams R, et al.: RTOG 9704 a phase III study of adjuvant pre and post chemoradiation (CRT) 5-FU vs. gemcitabine (G) for resected pancreatic adenocarcinoma. [Abstract] J Clin Oncol 24 (Suppl 18): A-4007, 180s, 2006.

Study ID Numbers:	CDR0000066076, RTOG-9704, E-R9704, SWOG-R9704
Study First Received:	November 1, 1999
Last Updated:	March 28, 2009
ClinicalTrials.gov Identifier:	NCT00003216 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Neoplasms by Site
Therapeutic Uses
Gemcitabine
Endocrine Gland Neoplasms
Digestive System Neoplasms
Neoplasms by Histologic Type

Endocrine System Diseases
Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Fluorouracil
Pancreatic Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2009