RATIONALE: Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may help gemcitabine kill more cancer cells by making them more sensitive to the drug.

PURPOSE: Phase II trial to study the effectiveness of combining 3-AP with gemcitabine in treating patients who have unresectable or metastatic bile duct or gallbladder cancer.

Condition	Treatment or Intervention	Phase
unresectable extrahepatic bile duct cancer recurrent gallbladder cancer unresectable gallbladder cancer recurrent extrahepatic bile duct cancer adenocarcinoma of the extrahepatic bile duct	Drug: 3-AP  Drug: gemcitabine  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the objective response rate in patients with unresectable or metastatic biliary duct or gallbladder cancer treated with 3-AP (Triapine®) and gemcitabine.
• Determine the toxic effects and recovery from toxic effects of this regimen in these patients.
• Determine the survival and progression-free survival of patients treated with this regimen.

OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to bilirubin levels (normal vs abnormal).

Patients receive 3-AP (Triapine®) IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 1 additional course beyond CR.

Patients are followed every 3 weeks for up to 2 years.

PROJECTED ACCRUAL: A total of 31-78 patients (10-29 with liver dysfunction and 21-49 without liver dysfunction) will be accrued for this study within 10-24.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:
• Adenocarcinoma of the biliary duct
• Carcinoma of the ampulla of Vater
• Gallbladder cancer
• Unresectable or metastatic disease
• Measurable disease
• At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No glucose-6-phosphate dehydrogenase deficiency

Hepatic

• Bilirubin no greater than 3 times upper limit of normal

Renal

• Creatinine normal

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No uncontrolled pulmonary disease, including any of the following:
• Asthma
• Chronic bronchitis
• Chronic obstructive pulmonary disease
• No requirement for chronic oxygen use

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for the malignancy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• At least 4 weeks since prior definitive surgery and recovered
• Recovered from prior surgical biopsy

Other

• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
New York
      Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx,  New York,  10467,  United States; Recruiting
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Scott Wadler, MD,  Principal Investigator,  Cornell University Medical College   

Study ID Numbers:  CDR0000346767; NYWCCC-0803945; NCI-6254; NCT00075504
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075504
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08