Clinical trial NCT00075504: Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer
Official title: A Phase II Study of Triapine in Combination With Gemcitabine in Adenocarcinoma of the Biliary Ducts and Gall Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage II Gallbladder Cancer
Stage IIIA Gallbladder Cancer
Stage IIIB Gallbladder Cancer
Stage IVA Gallbladder Cancer
Stage IVB Gallbladder Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-01-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate According to RECIST Criteria
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Allyson Ocean
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ocean AJ, Christos P, Sparano JA, Matulich D, Kaubish A, Siegel A, Sung M, Ward MM, Hamel N, Espinoza-Delgado I, Yen Y, Lane ME. Phase II trial of the ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehydethiosemicarbazone plus gemcitabine in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol. 2011 Aug;68(2):379-88. doi: 10.1007/s00280-010-1481-z. Epub 2010 Oct 28.