GTX Regimen for Biliary Cancers

This study has been terminated.
(Poor patient accrual)
Sponsor:
Information provided by (Responsible Party):
Robert L. Fine, Columbia University
ClinicalTrials.gov Identifier:
NCT00868998
First received: March 23, 2009
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Biliary Cancer
Drug: Gemcitabine, docetaxel, and capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the Gemzar, Taxotere and Xeloda Regimen (GTX) for Inoperable or Metastatic Adenocarcinoma of the Biliary System

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Response rate [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Toxicity [ Time Frame: Prior to day 4 and on day 12 ] [ Designated as safety issue: Yes ]

Enrollment: 4
Study Start Date: August 2005
Study Completion Date: October 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: Gemcitabine, docetaxel, and capecitabine
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
Other Names:
  • Gemzar
  • Taxotere
  • Xeloda

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the intrahepatic or extrahepatic biliary tract including cholangiocarcinoma, gallbladder cancer and ampullary cancer (ampula of vater).
  • Prior therapy with gemcitabine, Xeloda or docetaxel is acceptable if he/she only received and failed one of the 3 drugs.
  • Prior experimental drug therapies such as Phase I agents are acceptable.
  • Measurable disease: Any mass measurable by RECIST 1.1 parameters by CT or MRI scans of metastatic and primary tumor sites
  • Ineligible for other high priority national or institutional studies
  • Prior radiation and surgery allowed:

    • 3 weeks since surgery or last chemotherapy
    • 4 weeks since RT
  • Non pregnant females with a negative serum β-HCG test within 1 week of starting the study, who are not breast feeding. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.
  • Clinical Parameters Life expectancy > 3 months Age ≥ 18 y.o Performance status 0-2 (ECOG) (See Appendix IV) Peripheral Neuropathy must be ≤ grade 1 Able to tolerate oral chemotherapeutic medications
  • Required initial laboratory data

CBC with Differential Basic Metabolic Panel (BMP) Liver Function Tests (LFTs) Serum β-HCG (non-menopausal females) Tumor Specific Tests Hepatitis B and C Tests Pulse Oximetry on Room Air >90%

  • Informed Consent: Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts.

Exclusion Criteria:

  • Hypersensitivity: Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 must be excluded.
  • Prior malignancy in last 5 years other than: curatively treated carcinoma in-situ of the cervix, non-melanoma skin cancer, DCIS (ductal carcinoma in situ) or early stage (I or II) prostate cancer previously treated with curative intent by radiation and/or surgery and is now cancer free.
  • Known serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g., serious infection).
  • Patients with CNS metastases shall be excluded.
  • Patients with compromised immune systems are at increased risk of toxicity and lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive patients are excluded from the study.
  • Patients with currently active inflammatory bowel disease (ulcerative colitis, Crohn's) or sclerosing cholangitis will be excluded. A history of these IBD's or sclerosing cholangitis is acceptable if the disease is in remission or quiescent.
  • Active infection with non-A hepatitis virus (Hepatitis B and C) will be excluded
  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: NCT00868998

Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Robert L Fine, MD Columbia University
  More Information

No publications provided

Responsible Party: Robert L. Fine, Associate Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center, Columbia University
ClinicalTrials.gov Identifier: NCT00868998     History of Changes
Other Study ID Numbers: AAAB3329
Study First Received: March 23, 2009
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Capecitabine
Docetaxel
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
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 29, 2014