RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective, or whether chemotherapy is more effective than observation, in treating pancreatic cancer after surgery.

PURPOSE: Phase III trial to compare the effectiveness of two chemotherapy regimens with no further therapy in treating patients who have completely resected pancreatic cancer.

Condition	Treatment or Intervention	Phase
acinar cell adenocarcinoma of the pancreas duct cell adenocarcinoma of the pancreas stage I pancreatic cancer stage II pancreatic cancer stage III pancreatic cancer stage IVA pancreatic cancer	Drug: fluorouracil  Drug: gemcitabine  Drug: leucovorin calcium  Procedure: adjuvant therapy  Procedure: chemotherapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the efficacy of adjuvant gemcitabine vs fluorouracil and leucovorin calcium (vs observation only in patients with ampullary or other pancreatic malignancy), in terms of 2-year survival rate, in patients with completely resected pancreatic cancer.

Secondary

• Compare the toxicity of these regimens in these patients.
• Compare the quality of life and 5-year survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (ductal adenocarcinoma vs ampullary or other pancreatic malignancy), resection margin status, and participating country. Patients are randomized to 1 of 2 treatment arms. Randomization for patients with ampullary or other pancreatic malignancy includes an observation arm.

• Arm I: Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15.
• Arm III (patients with ampullary or other pancreatic malignancy only): Patients undergo observation. Treatment in arms I and II repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 3, 6, and 12 months, and then annually for 5 years.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 660 patients with pancreatic adenocarcinoma (330 per arms I and II) will be accrued for this study within 5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed ductal adenocarcinoma of the pancreas OR
• Histologically confirmed diagnosis of 1 of the following types of cancer:
• Acinar cell carcinoma or cystadenocarcinoma of the pancreas
• Cancers of the periampullary region
• Cancers of the intrapancreatic part of the bile duct
• Periampullary cancers of uncertain origin
• Complete macroscopic resection (R0 or R1 resection)
• Histological examination of all resection margins required
• No stage IVB disease
• No evidence of malignant ascites
• No liver or peritoneal metastases
• No evidence of spread to other distant abdominal or extra-abdominal organs
• No pancreatic lymphoma

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant
• Able to participate in long-term follow-up
• No other prior or concurrent malignancy except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
• No serious medical or psychological condition that would preclude study treatment

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No neoadjuvant chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• Recovered from prior resection

Australia, New South Wales
      Institute of Oncology at Prince of Wales Hospital, Randwick,  New South Wales,  2031,  Australia; Recruiting
Australia, South Australia
      Flinder Medical Centres, Bedford Park,  South Australia,  5042,  Australia; Recruiting
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada; Recruiting
Canada, British Columbia
      British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna,  British Columbia,  V1Y 5L3,  Canada; Recruiting
      British Columbia Cancer Agency - Vancouver Island Cancer Centre, Victoria,  British Columbia,  V8R 6V5,  Canada; Recruiting
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada; Recruiting
Canada, Nova Scotia
      Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada; Recruiting
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
      Cancer Centre of Southeastern Ontario, Kingston,  Ontario,  K7L 5P9,  Canada; Recruiting
      Grand River Regional Cancer Centre at Grand River Hospital, Kitchner,  Ontario,  N2G 1G3,  Canada; Recruiting
      Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus, Ottawa,  Ontario,  K1H 8L6,  Canada; Recruiting
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting
      St. Joseph's Health Centre - Toronto, Toronto,  Ontario,  M6R 1B5,  Canada; Recruiting
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada; Recruiting
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada; Recruiting
Canada, Quebec
      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada; Recruiting
      McGill Cancer Centre, Montreal,  Quebec,  H2W 1S6,  Canada; Recruiting
Czech Republic
      Institute for Clinical and Experimental Medicine, Preha 4,  14021,  Czech Republic; Recruiting
Finland
      Tampere University Hospital, Tampere,  33521,  Finland; Recruiting
France
      Hopital Tenon, Paris,  75970,  France; Recruiting
Germany
      Universitaets-Kinderklinik Heidelberg, Heidelberg,  D-69120,  Germany; Recruiting
Greece
      Agia Olga Hospital, Athens,  G-15233,  Greece; Recruiting
Hungary
      Mav Hospital, Budapest,  1062,  Hungary; Recruiting
Italy
      Policlinico Borgo Roma, Verona,  37134,  Italy; Recruiting
Sweden
      Uppsala University Hospital, Uppsala,  S-75185,  Sweden; Recruiting
Switzerland
      University of Bern, Bern,  CH-3012,  Switzerland; Recruiting
United Kingdom, England
      Royal Liverpool University Hospital, Liverpool,  England,  L69 3GA,  United Kingdom; Recruiting

Study chairs or principal investigators

John P. Neoptolemos, MD,  Study Chair,  Royal Liverpool University Hospital   
Malcolm J. Moore, MD,  Study Chair,  Princess Margaret Hospital   
R. Padbury,  Flinder Medical Centres   
David Goldstein, MD,  Institute of Oncology at Prince of Wales Hospital   

Study ID Numbers:  CDR0000287023; NCRI-ESPAC-3; EU-20043; CAN-NCIC-PA2; AGITG-ESPAC-3; NCT00058201
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00058201
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08