Fluorouracil, Gemcitabine, and Radiation Therapy in Treating Patients With Cancer of the Pancreas

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003216
• Other study ID #: RTOG-9704
• Secondary ID: CDR0000066076E-R
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: November 18, 2013
• Start date: July 1998

Study information

• Verified date: November 2013
• Source: Radiation Therapy Oncology Group
• 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 518
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• fluorouracil

• gemcitabine hydrochloride

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Medical Center	Boston	Massachusetts
United States	Western New York Urology Associates	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Barrett Cancer Center	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Veterans Affairs Medical Center - Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	Mayo Clinic	Jacksonville	Florida
United States	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts
United States	CCOP - Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	CCOP - Dayton	Kettering	Ohio
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Veterans Affairs Medical Center - West Los Angeles	Los Angeles	California
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	MBCCOP - LSU Medical Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	St. Vincents Comprehensive Cancer Center	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	CCOP - Greater Phoenix	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)	Phoenix	Arizona
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Oregon Cancer Institute	Portland	Oregon
United States	Veterans Affairs Medical Center - Portland	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	University of California Davis Medical Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Hospital - Southfield	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Northwest	Tacoma	Washington
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Eastern Cooperative Oncology Group, National Cancer Institute (NCI), Southwest Oncology Group

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (17)

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.

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.

Abrams RA, Winter KA, Regine WF, Safran H, Hoffman JP, Lustig R, Konski AA, Benson AB, Macdonald JS, Rich TA, Willett CG. Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704--a phase III — View Citation

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 va — View Citation

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.

Berger AC, Winter K, Hoffman JP, Regine WF, Abrams RA, Safran H, Freedman GM, Benson AB 3rd, Macdonald J, Willett CG. Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 =90 U/mL and comparison to the CONKO-001 trial. Int J Radiat Onco — View Citation

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 Canc

Farrell JJ, Bae K, Wong J, Guha C, Dicker AP, Elsaleh H. Cytidine deaminase single-nucleotide polymorphism is predictive of toxicity from gemcitabine in patients with pancreatic cancer: RTOG 9704. Pharmacogenomics J. 2012 Oct;12(5):395-403. doi: 10.1038/t — View Citation

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. Gastroente — View Citation

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 Gastrointes

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. [Abs

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,

Regine WF, Winter KA, Abrams R, Safran H, Hoffman JP, Konski A, Benson AB, Macdonald JS, Rich TA, Willett CG. Fluorouracil-based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5-year analy — View Citation

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 foll — View Citation

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.

Showalter TN, Winter KA, Berger AC, Regine WF, Abrams RA, Safran H, Hoffman JP, Benson AB, MacDonald JS, Willett CG. The influence of total nodes examined, number of positive nodes, and lymph node ratio on survival after surgical resection and adjuvant ch — View Citation

Tempero MA, Winter KA, Kim GE, et al.: S100A2 as a prognostic marker in patients receiving adjuvant therapy for pancreatic cancer (PC): A secondary analysis of RTOG 9704. [Abstract] J Clin Oncol 29 (Suppl 15): A-4118, 2011.

* Note: There are 17 references in all — Click here to view all references