• Objective response [ Designated as safety issue: No ]
  

• Pharmacokinetics [ Designated as safety issue: No ]
  
• Progression-free and overall survival [ Designated as safety issue: No ]
  

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 months 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.

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 to 90

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