Clinical trial NCT00024427: Triacetyluridine and Fluorouracil Compared With Gemcitabine in Treating Patients With Unresectable Locally Advanced, or Metastatic Pancreatic Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Drug/Agent Toxicity by Tissue/Organ
Pancreatic Cancer
Keywords: 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
Lead sponsor: Wellstat Therapeutics
Sponsor class: INDUSTRY
First posted: 2003-01-27
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Open Label Randomized Phase 3 Multi-Center Trial of PN401 plus high dose 5-FU versus Gemcitabine in Advanced Pancreatic Cancer Patients
timeFrame: Disease progression
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brookwood Medical Center
state: Alabama
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: Scripps Cancer Center at Scripps Clinic
state: California
city: Coral Springs
country: United States
facility: Northwest Oncology and Hematology Associates
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - World Plaza
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Florida Oncology Associates - South Side
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Institute - New Port Richey
state: Florida
city: Savannah
country: United States
facility: St. Joseph's Hospital
state: Georgia
city: New Albany
country: United States
facility: Cancer Care Center
state: Indiana
city: Baltimore
country: United States
facility: Cancer Center at Greater Baltimore Medical Center
state: Maryland
city: Gaithersburg
country: United States
facility: Wellstat Therapeutics
state: Maryland
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Jefferson City
country: United States
facility: Capitol Comprehensive Cancer Care Clinic
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Research and Treatment Center
state: New Mexico
city: Fresh Meadows
country: United States
facility: Queens Medical Associates, PC
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Akron
country: United States
facility: Summit Oncology Associates
state: Ohio
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase - Temple Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Eastside
state: South Carolina
city: Corpus Christi
country: United States
facility: Corpus Christi Cancer Center
state: Texas
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre at Ottawa Hospital - General Campus
state: Ontario
city: Thunder Bay
country: Canada
facility: Regional Cancer Care at Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Wellstat Therapeutics
name: Lenny Smith, MS
role: STUDY_CHAIR
References: