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

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 3


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

Drug Information available for: Fluorouracil Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by Radiation Therapy Oncology Group:


Estimated Enrollment:	518
Study Start Date:	July 1998
Primary Completion Date:	October 2005 (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 (Adult, Senior)
Sexes Eligible for Study:	All
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Show 107 Study Locations

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	Beth Israel Comprehensive Cancer Center - West Side Campus

More Information

Publications:

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 trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):809-16. doi: 10.1016/j.ijrobp.2010.11.039. Epub 2011 Feb 1.

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 Oncol Biol Phys. 2012 Nov 1;84(3):e291-7. doi: 10.1016/j.ijrobp.2012.04.035. Epub 2012 Jun 9.

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/tpj.2011.22. Epub 2011 May 31.

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 analysis of the U.S. Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011 May;18(5):1319-26. doi: 10.1245/s10434-011-1630-6. Epub 2011 Mar 10.

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 chemoradiation for pancreatic cancer: a secondary analysis of RTOG 9704. Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1328-35. doi: 10.1016/j.ijrobp.2010.07.1993. Epub 2010 Oct 8.

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.

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. doi: 10.1053/j.gastro.2008.09.067. 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 Dec 20;26(36):5918-22. doi: 10.1200/JCO.2008.18.6288. Epub 2008 Nov 24.

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. doi: 10.1001/jama.299.9.1019. Erratum in: JAMA. 2008 Apr 23/30;299(16):1902.

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.


Responsible Party:	Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:	NCT00003216 History of Changes
Other Study ID Numbers:	RTOG-9704 CDR0000066076 E-R9704 SWOG-R9704
Study First Received:	November 1, 1999
Last Updated:	November 18, 2013

Keywords provided by Radiation Therapy Oncology Group:


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

Additional relevant MeSH terms:


Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Fluorouracil	Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 23, 2017