Title

Triacetyluridine and Fluorouracil Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced, or Metastatic Pancreatic Cancer
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
  • Phase

    Phase 3
  • Study Type

    Interventional
  • Status

    Completed No Results Posted
  • Study Participants

    250
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more tumor cells. Chemoprotective drugs such as triacetyluridine may protect normal cells from the side effects of chemotherapy. It is not yet known which chemotherapy regimen is more effective in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus triacetyluridine with that of gemcitabine in treating patients who have locally advanced or metastatic pancreatic cancer that cannot be treated with surgery.
OBJECTIVES:

Compare the survival of patients with unresectable locally advanced or metastatic pancreatic cancer treated with triacetyluridine and high-dose fluorouracil vs gemcitabine.
Compare the time to tumor progression, overall response rate, and response duration in patients treated with these regimens.
Compare the safety of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease stage (II or III vs IV). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive high-dose fluorouracil (5-FU) IV over 30 minutes once weekly on weeks 1-3 followed by 1 week of rest. After each dose of 5-FU, patients receive oral triacetyluridine every 8 hours for a total of 8 doses. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive gemcitabine IV over 30 minutes once weekly on weeks 1-7 followed by 1 week of rest (course 1). Subsequent courses are given on weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 260 patients (130 per treatment arm) will be accrued for this study within 30 months.
Study Started
Feb 28
2001
Primary Completion
Feb 28
2006
Last Update
Jun 28
2012
Estimate

Drug fluorouracil

High dose 5-FU

  • Other names: 5-FU

Drug gemcitabine hydrochloride

Normal dose to treat pancreatic cancer

  • Other names: Gemzar

Drug triacetyluridine

6 grams (12 tablets)

  • Other names: 2',3',5'tri-O-acetyluridine

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
No Results Posted