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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00024427
• Other study ID #: CDR0000068931
• Secondary ID: WELLSTAT-401.00.
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2001
• Last updated: June 27, 2012
• Start date: February 2001

Study information

• Verified date: May 2010
• Source: Wellstat Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Drug/Agent Toxicity by Tissue/Organ
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• fluorouracil
High dose 5-FU
• gemcitabine hydrochloride
Normal dose to treat pancreatic cancer
• triacetyluridine
6 grams (12 tablets)

Locations

Country	Name	City	State
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Regional Cancer Care at Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
United States	Summit Oncology Associates	Akron	Ohio
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Cancer Center at Greater Baltimore Medical Center	Baltimore	Maryland
United States	Brookwood Medical Center	Birmingham	Alabama
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Northwest Oncology and Hematology Associates	Coral Springs	Florida
United States	Corpus Christi Cancer Center	Corpus Christi	Texas
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Florida Cancer Specialists - World Plaza	Fort Myers	Florida
United States	Queens Medical Associates, PC	Fresh Meadows	New York
United States	Wellstat Therapeutics	Gaithersburg	Maryland
United States	Cancer Centers of the Carolinas - Eastside	Greenville	South Carolina
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Florida Oncology Associates - South Side	Jacksonville	Florida
United States	Capitol Comprehensive Cancer Care Clinic	Jefferson City	Missouri
United States	Scripps Cancer Center at Scripps Clinic	La Jolla	California
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Cancer Care Center	New Albany	Indiana
United States	Florida Cancer Institute - New Port Richey	New Port Richey	Florida
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	Fox Chase - Temple Cancer Center	Philadelphia	Pennsylvania
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	St. Joseph's Hospital	Savannah	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Wellstat Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Open Label Randomized Phase 3 Multi-Center Trial of PN401 plus high dose 5-FU versus Gemcitabine in Advanced Pancreatic Cancer Patients		Disease progression	No