Triapine and Gemcitabine Hydrochloride in Treating Patients With Bile Duct or Gallbladder Cancer That is Metastatic or Cannot Be Removed By Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00075504
First received: January 9, 2004
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Extrahepatic Bile Duct
Metastatic Extrahepatic Bile Duct Cancer
Stage II Gallbladder Cancer
Stage IIIA Gallbladder Cancer
Stage IIIB Gallbladder Cancer
Stage IVA Gallbladder Cancer
Stage IVB Gallbladder Cancer
Unresectable Extrahepatic Bile Duct Cancer
Drug: triapine
Drug: gemcitabine hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Triapine in Combination With Gemcitabine in Adenocarcinoma of the Biliary Ducts and Gall Bladder

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate according to RECIST criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: November 2003
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (triapine, gemcitabine hydrochloride)
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 CR receive 1 additional course beyond CR.
Drug: triapine
Given IV
Other Names:
  • 3-AP
  • OCX-191
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

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 bilary 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients must have 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
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension with the longest diameter to be recorded as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Patients may not have had prior chemotherapy for their disease; if patients have had prior definitive surgery or prior radiation therapy, they must have fully recovered from the effects of therapy with at least 4 weeks recovery time; for patients who have had surgical biopsy only, they must have simply recovered
  • 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)
  • The effects of Triapine on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because heterocyclic carboxaldehyde thiosemicarbazones as well as other therapeutic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • When possible, patients should have an aspiration of the tumor before beginning treatment and 24 hours after treatment has started
  • 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 women are excluded from this study because Triapine is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Triapine, breastfeeding should be discontinued if the mother is treated with Triapine; these potential risks may also apply to other agents used in this study
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Triapine or gemcitabine administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075504

Locations
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Sponsors and Collaborators
Investigators
Principal Investigator: Allyson Ocean Montefiore Medical Center
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075504     History of Changes
Other Study ID Numbers: NCI-2012-03030, 0803-945, 6254, U01CA062505, N01CM62201, N01CM62204
Study First Received: January 9, 2004
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Gallbladder Neoplasms
Bile Duct Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Bile Duct Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 14, 2014