Triacetyluridine And Fluorouracil Compared With Gemcitabine In Treating Patients With Unresectable Locally Advanced, Or Metastatic Pancreatic Cancer

Study Overview

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

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.

Drug/Agent Toxicity by Tissue/Organ
Pancreatic Cancer

DRUG: fluorouracil
DRUG: gemcitabine hydrochloride
DRUG: triacetyluridine

CDR0000068931
WELLSTAT-401.00.001
PRONEURON-401.00.001
UAB-0105
UAB-F010524008

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2001-09-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-06-27
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-06-28
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2010-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Karnofsky 70-100%

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Lenny Smith, MS, Wellstat Therapeutics

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record