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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00024427
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 28, 2012
Information provided by (Responsible Party):
Wellstat Therapeutics

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Drug/Agent Toxicity by Tissue/Organ Pancreatic Cancer Drug: fluorouracil Drug: gemcitabine hydrochloride Drug: triacetyluridine Phase 3

Detailed Description:


  • 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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2001
Actual Primary Completion Date : February 2006

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: fluorouracil
    High dose 5-FU
    Other Name: 5-FU
  • Drug: gemcitabine hydrochloride
    Normal dose to treat pancreatic cancer
    Other Name: Gemzar
  • Drug: triacetyluridine
    6 grams (12 tablets)
    Other Name: 2',3',5'tri-O-acetyluridine

Primary Outcome Measures :
  1. Open Label Randomized Phase 3 Multi-Center Trial of PN401 plus high dose 5-FU versus Gemcitabine in Advanced Pancreatic Cancer Patients [ Time Frame: Disease progression ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status:

  • Karnofsky 70-100%

Life expectancy:

  • At least 3 months


  • WBC at least 3,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.5 g/dL


  • 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


  • Creatinine less than 2.0 mg/dL
  • No uncontrolled renal dysfunction


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

    • Angina
    • Arrhythmias
    • Uncompensated cardiac failure
    • Myocardial infarction within the past 6 months


  • No uncontrolled pulmonary dysfunction


  • Able to take and/or retain oral medication
  • No uncontrolled malabsorption syndrome or any other condition that would interfere with intestinal absorption


  • 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


Biologic therapy:

  • No concurrent biologic therapy (including immunotherapy) for cancer


  • 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


  • Prior radiotherapy allowed
  • No concurrent radiotherapy


  • See Disease Characteristics
  • Prior resection of pancreas allowed


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00024427

  Show 29 Study Locations
Sponsors and Collaborators
Wellstat Therapeutics
Study Chair: Lenny Smith, MS Wellstat Therapeutics

Responsible Party: Wellstat Therapeutics Identifier: NCT00024427     History of Changes
Other Study ID Numbers: CDR0000068931
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 28, 2012
Last Verified: May 2010

Keywords provided by Wellstat Therapeutics:
drug/agent toxicity by tissue/organ
stage II pancreatic cancer
stage III pancreatic cancer
recurrent pancreatic cancer
adenocarcinoma of the pancreas
stage IV pancreatic cancer

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