Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer

Phase 2

Completed

Conditions: Stage IVA Gallbladder Cancer
Stage II Gallbladder Cancer
Stage IIIA Gallbladder Cancer
Stage IVB Gallbladder Cancer
Stage IIIB Gallbladder Cancer

Brief Summary: This phase II trial is studying how well giving 3-AP together with gemcitabine works in treating patients with unresectable or metastatic bile duct or gallbladder cancer. 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.

Detailed Description: OBJECTIVES:

I. To determine the objective response rates for the combination of triapine and gemcitabine in patients with primary tumors of the biliary ducts and gall bladder.

II. To assess the toxicities and recovery from toxicities for patients with biliary duct and gall bladder tumors treated with the combination of triapine and gemcitabine.

III. To determine the survival and progression free survival of patients with biliary and gall bladder tumors treated with the combination of triapine and gemcitabine.

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.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the biliary ducts that is unresectable and/or metastatic; this can include unresectable or metastatic carcinomas of the Ampulla of Vater. In addition, unresectable or metastatic gall bladder carcinoma will be allowed
Measurable disease
No prior chemotherapy
Life expectancy of greater than 3 months
ECOG performance status =< 2 (Karnofsky >= 60%)
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Creatinine within normal institutional limits
Patients may have mildly abnormal liver function defined as a total bilirubin > ULN and =< 3x the institutional upper limits of normal (includes CTCAE v.3 grades 1-2 hyperbilirubinemia)
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients may not be receiving any other investigational agents
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Triapine or gemcitabine
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
Uncontrolled pulmonary disease including asthma, chronic bronchitis and COPD or with requirements for chronic oxygen use
Pregnant or lactating women
HIV infection
Patients with G6PD deficiency will be excluded in view of the potential for methemoglobinemia
Psychiatric illness/social situations that would limit compliance with study requirements

Arm && Interventions

Group	Intervention	Description
triapine, gemcitabine	triapine	Triapine IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15, repeat every 28 days
triapine, gemcitabine	gemcitabine	Triapine IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15, repeat every 28 days

Primary Outcome Measures

Name	Time	Method
Response Rate According to RECIST Criteria	Up to 2 years	Tumor response was assessed every eight weeks by CT scan using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disapperance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall response (OR) = CR+PR.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	Up to 2 years	PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Overall Survival	Up to 2 years