An Open Label, Randomized, Controlled, Phase III, Multi-center, Clinical Trial Of PN401 With High Dose 5-Fluorouracil (5FU) Versus Gemcitabine For Treatment Of Patients With Advanced Pancreatic Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the pancreas

- Unresectable locally advanced or metastatic disease

- Stage II, III, or IV

- Measurable or evaluable disease

- No elevated tumor marker (CA 19-9) only

- No clinically significant third-space fluid accumulation (e.g., ascites or pleural
effusion)

- No carcinoid, islet cell, or lymphoma of the pancreas

- No prior or concurrent brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 70-100%

Life expectancy:

- At least 3 months

Hematopoietic:

- WBC at least 3,500/mm^3

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

- Hemoglobin at least 9.5 g/dL

Hepatic:

- Bilirubin no greater than 2.0 mg/dL

- ALT or AST less than 3 times upper limit of normal (ULN) (5 times ULN if liver
metastases present)

- No uncontrolled hepatic dysfunction

Renal:

- Creatinine less than 2.0 mg/dL

- No uncontrolled renal dysfunction

Cardiovascular:

- No uncontrolled cardiovascular disease requiring therapy, including the following:

- Angina

- Arrhythmias

- Uncompensated cardiac failure

- Myocardial infarction within the past 6 months

Pulmonary:

- No uncontrolled pulmonary dysfunction

Gastrointestinal:

- Able to take and/or retain oral medication

- No uncontrolled malabsorption syndrome or any other condition that would interfere
with intestinal absorption

Other:

- No known allergy to fluorouracil (5-FU), gemcitabine, triacetyluridine, or any of
their components

- No dihydropyrimidine-dehydrogenase deficiency

- No active uncontrolled infection

- No uncontrolled neurologic or psychiatric dysfunction

- No other malignancy except previously resected basal cell cancer or curatively
resected stage I or less cervical cancer that has been disease free for at least 5
years

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent biologic therapy (including immunotherapy) for cancer

Chemotherapy:

- No prior chemotherapy for cancer other than as a radiosensitizer

- No prior 5-FU or gemcitabine other than as a radiosensitizer

- No prior triacetyluridine

- No other concurrent chemotherapy (including leucovorin calcium) for cancer

Endocrine therapy:

- No concurrent hormonal therapy for cancer

- Concurrent megestrol, oral contraceptives, or postmenopausal estrogen replacement
therapy allowed

Radiotherapy:

- Prior radiotherapy allowed

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

- Prior resection of pancreas allowed

Other:

- At least 30 days since prior investigational drug or therapeutic device

- No other concurrent anticancer therapy

- No other concurrent investigational drugs or devices

- No concurrent drugs that would interact adversely with 5-FU or gemcitabine