Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Stage IVA Gallbladder Cancer

Stage IIIA Gallbladder Cancer

Stage IIIB Gallbladder Cancer

Stage II Gallbladder Cancer

Stage IVB Gallbladder Cancer

Treatments

Drug: triapine

Drug: gemcitabine

Study type

Interventional

Funder types

NIH

Identifiers

NCT00075504

U01CA062505 (U.S. NIH Grant/Contract)

NCI-2012-03030

N01CM62204 (U.S. NIH Grant/Contract)

6254 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

33 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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