GTX Regimen for Biliary Cancers

Biliary Cancer Clinical Trial

Official title: Phase II Study of the Gemzar, Taxotere and Xeloda Regimen (GTX) for Inoperable or Metastatic Adenocarcinoma of the Biliary System

Status Terminated

Clinical Trial Summary

This is a study for patients with advanced cancer of the biliary tree, such as cholangiocarcinoma. They will be treated with a chemotherapy regimen consisting of Gemcitabine, Taxotere, and Xeloda every 21 days for at least 9 weeks. Treatment will continue until their cancer progresses. This chemotherapy regimen has been used in pancreatic cancer and there is reason to believe that it will be effective for cancers of the biliary tree as well.

Clinical Trial Description

After initial presentation of our data concerning this regimen (in pancreatic cancer) at the 2003 and 2004 ASCO meetings, a number of practitioners began using the regimen for pancreatic cancer patients. More importantly, several of these investigators began using the same regimen for patients with unresectable and metastatic biliary tree cancers, such as cholangiocarcinoma. In personal communications with us, they have cited the absence of reasonable alternatives as the primary reason to experiment with novel regimens. They have described to us case reports, whereby patients with cholangiocarcinoma had objective responses to this regimen. Personally, our group, in a pilot study, has treated 5 patients with the GTX regimen, and has documented 3 partial responses and 1 stable disease in 3 patients afflicted with cholangiocarcinoma and 2 with gall bladder cancer. In this prospective study (to date 08/09), three patients have been enrolled and two of them achieved a partial response, by RECIST parameters, of >30% reduction in tumor size by cycle 3 (the first evaluation point). Therefore, we believe that GTX will show efficacy in treating this disease.

Indeed, there is clinical evidence of efficacy of these drugs in cholangiocarcinomas. In a phase II trial, single agent gemcitabine produced a 30% partial response rate and a 30% stable disease rate in chemotherapy-naïve, cholangiocarcinoma patients.(8) A retrospective review of patients treated with combination fluorouracil (continuous infusion) and gemcitabine (30 minute infusion) demonstrated a 33% response rate and a 30% stable disease rate, with a median survival of 5.3 months. The low, observed rate of grade 3-4 myelosuppression (11%) suggests this is a well tolerated regimen.(9) Likewise, gemcitabine and docetaxel have been combined in the treatment of these cancers, resulting in a 33% response rate and a 36% stable disease rate (3). We hope to improve upon these studies by substituting a sixty minute infusion rate for gemcitabine instead of the traditional thirty minute infusion, and by substituting capecitabine for infused fluorouracil. In addition, we have tested the GTX regimen in 2 cell lines in our lab: one cholangiocarcinoma and one gall bladder human line. We found that when GTX is given all at once to the cells, there is no increased cytotoxicity, but when given in the amount and dosing sequence that mimics the GTX regimen of this protocol, there is significant synergistic cytotoxicity. This synergism produces approximately a 3-fold increase in cell kill as compared with any other combination of the drugs or from any single drug in the GTX regimen. Given our laboratory data in cholangiocarcinoma cell lines that demonstrates synergy between these drugs, we are optimistic that we can produce superior results with less toxicities. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Biliary Cancer
• Biliary Tract Neoplasms

• NCT number: NCT00868998
• Study type: Interventional
• Source: Columbia University
• Status: Terminated
• Phase: Phase 2
• Start date: August 2005
• Completion date: October 2010