Gemcitabine Plus High-Dose 5-Fu/Leucovorin in the Treatment of Advanced or Metastatic Carcinoma of the Biliary Tract

This study has been completed.
Sponsor:
Collaborators:
Chang Gung Memorial Hospital
Changhua Christian Hospital
China Medical University Hospital
Mackay Memorial Hospital
Chi Mei Medical Hospital
Taipei Veterans General Hospital, Taiwan
National Cheng-Kung University Hospital
National Taiwan University Hospital
Information provided by:
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT00201305
First received: September 13, 2005
Last updated: March 30, 2009
Last verified: September 2005
  Purpose

This is an open-label phase II trial with weekly gemcitabine plus high-dose 5-FU/leucovorin infusion (HDFL) for patients with advanced or metastatic carcinoma of the biliary tract. The primary endpoint is patients' response and the secondary endpoints are chemotherapy-related toxicity, time to disease progression and overall survival. .


Condition Intervention Phase
Biliary Tract Disease
Drug: Gemcitabine+5FU+Leucovorin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Phase II Randomized Trial-Weekly Gemcitabine Plus High-Dose 5-Fluorouracil/ Leucovorin in the Treatment of Advanced or Metastatic Carcinoma of the Biliary Tract

Resource links provided by NLM:


Further study details as provided by National Health Research Institutes, Taiwan:

Primary Outcome Measures:
  • To determine the response rate of weekly gemcitabine plus high-dose 5-FU/leucovorin chemotherapy for patients with advanced or metastatic biliary tract cancer.

Secondary Outcome Measures:
  • To determine:
  • 1.Toxicity profile of gemcitabine plus high-dose 5-FU/leucovorin chemotherapy for advanced or metastatic biliary tract cancer.
  • 2.Time to disease progression
  • 3.Overall survival
  • 4.Quality of life

Estimated Enrollment: 50
Study Start Date: July 2002
Estimated Study Completion Date: August 2012
Detailed Description:

5-FU has been the mainstay of chemotherapeutic agents for gastrointestinal malignancies. The use of weekly 24-hour infusion of HDFL produces high clinical response in a variety of cancers, including colorectal, gastric and breast cancers, with minimal chemotherapy-related toxicity. Gemcitabine is a synthesized deoxycytidine analogue that is metabolized to dFdCTP in tumor cells and results in inhibition of DNA synthesis and depletion of normal cellular nucleotide pool. It has been shown to be active in the treatment of pancreatic cancer and non-small cell lung cancer. Since the biliary tract and the pancreas share a common embryonic origin and cancers from both sites are characterized by resistance to most chemotherapeutic agents, we postulate that gemcitabine may also be effective for cancer of the biliary tract. In our institution we have devised a regimen of weekly gemcitabine and 24-hour infusion of HDFL for patients with advanced or metastatic pancreatic adenocarcinoma. In 18 evaluable patients, 2 achieved a partial response and 3 minor response. The median duration of response was 4 months and the treatment-related toxicity was acceptable.

The eligibility criteria are patients with advanced or metastatic carcinoma of the biliary tract who are not candidates for curative surgical treatment; good performance status; no prior chemotherapy; clinical measurable tumor; good organ function and good compliance. Each cycle of chemotherapy consists of 4 weeks. On days 1, 8 and 15, gemcitabine will be given by 30-minute intravenous infusion and 5-FU and leucovorin by 24-hour continuous intravenous infusion. The dose of gemcitabine will be 1000 mg/m2. The doses of 5-FU will be 2000 mg/m2 and leucovorin, 300 mg/m2. Treatment will continue until disease progresses or prohibitive toxicity develops. For patients with complete response (CR), chemotherapy will continue for 3 additional courses after the documentation of CR. Estimated time for patient accrual is 3 years.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Histologically proven carcinoma of the biliary tract, including gallbladder carcinoma and cholangiocarcinoma. The disease should be either locally advanced to the extent that curative surgery is impossible or with documented distant metastasis.
  2. Bi-dimensionally measurable disease by physical examination or image study (roentgenogram or computed tomography (CT) scan).
  3. Age > 18 years. For patients older than 70 years of age, detailed evaluation of the organ function reserves must be done before enrollment unto protocol treatment.
  4. Karnofsky performance status> 60%
  5. Adequate bone marrow reserves, defined as white blood cell (WBC)>4,000/ml, absolute neutrophil count (ANC)> 1,500/ml, platelet> 150,000/ml.
  6. Liver transaminases <5 times upper normal limits; total bilirubin <3 mg/dl; serum creatinine < 1.5 mg/dl
  7. Serum triglyceride level >70 mg/dl
  8. No prior cytotoxic chemotherapy. Previous radiotherapy is allowed if the treatment was completed at least 6 weeks before the enrollment onto this study.
  9. Patients of childbearing age should have effective contraception during the study period.
  10. All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional guidelines.

Exclusion criteria:

  1. Patients who are receiving concurrent radiotherapy, chemotherapy or other experimental therapy.
  2. Patients who refuse port-A catheter implantation
  3. Patients with brain or leptomeningeal metastases.
  4. Patients who have significant cardiac arrhythmia or acute myocardial infarction within 6 months before entry.
  5. Patients who have major systemic diseases that the attending physicians considered inappropriate for systemic chemotherapy.
  6. Life expectancy less than 2 months.
  7. Pregnant or nursing women may not participate. Women or men with reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  8. Patients who have previous malignancy except for the following: adequately treated basal cell or squamous cell skin cancers, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any cancer from which the patient has been disease-free for 5 years.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00201305

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Health Research Institutes, Taiwan
Chang Gung Memorial Hospital
Changhua Christian Hospital
China Medical University Hospital
Mackay Memorial Hospital
Chi Mei Medical Hospital
Taipei Veterans General Hospital, Taiwan
National Cheng-Kung University Hospital
National Taiwan University Hospital
Investigators
Study Chair: Ann-Li Cheng, PHD National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00201305     History of Changes
Other Study ID Numbers: T3202
Study First Received: September 13, 2005
Last Updated: March 30, 2009
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Biliary Tract Diseases
Carcinoma
Digestive System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Levoleucovorin
Gemcitabine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014