Clinical trial NCT00868998
Conditions: Biliary Cancer
Keywords: Biliary Cancer
Sponsor: Columbia University
Start date: 2005-08-01; Completion date: 2010-10-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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.

Arms: arm 1: Gemcitabine, docetaxel, and capecitabine
Interventions: intervention 1: Gemcitabine, docetaxel, and capecitabine
Intervention descriptions: intervention 1: Day 1-14: Capecitabine 600 mg/m2/day (maximum dose 2000 mg/m2/day total divided into BID PO doses) Day 4 and 11: Gemcitabine 600 mg/m2 IV over 60 mins Day 4 and 11: Docetaxel 30 mg/m2 IV over 60 mins preceded by 12 mg dexamethasone IV or PO or 4 mg if diabetic

Protocol documents: