Gemcitabine With or Without Capecitabine in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

A Phase III Multicenter Randomized Clinical Trial Comparing Gemcitabine Alone Or In Combination With Capecitabine For The Treatment Of Patients With Advanced Pancreatic Cancer

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 if gemcitabine is more effective with or without capecitabine in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without capecitabine in treating patients who have locally advanced or metastatic pancreatic cancer.

OBJECTIVES:

• Compare the 1-year survival rate of patients with locally advanced or metastatic pancreatic cancer treated with gemcitabine with or without capecitabine.
• Compare the median and 2-year survival rates and the objective response rates of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is an randomized, open-label, multicenter study. Patients are stratified according to disease stage (locally advanced vs metastatic) and performance status (0 and 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 during the first course. After a 1-week rest period, patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15. Subsequent courses repeat every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 3 months for 1 year, and then annually thereafter.

Patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 508 patients (254 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed ductal adenocarcinoma of the pancreas

  • Locally advanced or metastatic disease not amenable to curative surgical resection
  • Macroscopic residual disease after prior resection with histological confirmation is allowed

• Unidimensionally measurable disease

• No intracerebral metastases or meningeal carcinomatosis

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• WHO 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC greater than 3,000/mm3
• Neutrophil count greater than 1,500/mm3
• Platelet count greater than 100,000/mm3

Hepatic:

• Bilirubin less than 2 mg/dL

Renal:

• Creatinine less than 2 mg/dL
• Creatinine clearance greater than 50 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No uncontrolled angina pectoris

Other:

• No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other concurrent uncontrolled medical condition
• No other medical or psychiatric condition that would preclude study
• No known hypersensitivity to fluorouracil
• No dihydropyrimidine dehydrogenase deficiency
• No known malabsorption syndromes
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy (including preoperative or adjuvant) for this disease
• No other concurrent cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy (including preoperative or adjuvant) for this disease

Surgery:

• See Disease Characteristics

Other:

• No prior investigational drugs (including preoperative or adjuvant) for this disease
• No other concurrent investigational drugs
• No concurrent dipyridamole or allopurinol
• No concurrent sorivudine or sorivudine analogs (e.g., brivudine) (capecitabine arm only)