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Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer

Primary Purpose

Stage II Gallbladder Cancer, Stage IIIA Gallbladder Cancer, Stage IIIB Gallbladder Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
triapine
gemcitabine
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage II Gallbladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

  • Montefiore Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

triapine, gemcitabine

Arm Description

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

Outcomes

Primary Outcome Measures

Response Rate According to RECIST Criteria
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

Progression Free Survival
PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Overall Survival

Full Information

First Posted
January 9, 2004
Last Updated
August 31, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00075504
Brief Title
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

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
November 2003 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage II Gallbladder Cancer, Stage IIIA Gallbladder Cancer, Stage IIIB Gallbladder Cancer, Stage IVA Gallbladder Cancer, Stage IVB Gallbladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
triapine, gemcitabine
Arm Type
Experimental
Arm Description
Triapine IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15, repeat every 28 days
Intervention Type
Drug
Intervention Name(s)
triapine
Other Intervention Name(s)
3-AP, OCX-191
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Other Intervention Name(s)
dFdC, difluorodeoxycytidine hydrochloride, Gemzar
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Response Rate According to RECIST Criteria
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Time Frame
Up to 2 years
Title
Overall Survival
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allyson Ocean
Organizational Affiliation
Montefiore Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20981545
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.
Results Reference
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Triapine and Gemcitabine Hydrochloride in Gallbladder Cancer

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