Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

This study has been completed.
Sponsor:
Collaborator:
Henrik Jensen, Dept. of Oncology, Vejle Sygehus, Vejle, Denmark
Information provided by:
Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT00350961
First received: July 10, 2006
Last updated: August 25, 2008
Last verified: August 2008
  Purpose

In Denmark approximately 200 new cases of cholangiocarcinoma are diagnosed every year. No standard treatment exists for patients with advanced cholangiocarcinoma, and improved systemic treatments are needed.

Duplets of gemcitabine, oxaliplatin and capecitabine have been evaluated in various cancers and several different regimens are well tolerated and active, especially in upper gastrointestinal cancers, exocrine pancreatic cancer and non-small cell lung cancer.

The triplet combination of these agents has not been studied, but a triplet combination of gemcitabine, oxaliplatin and 5-FU infusion has been evaluated in a phase I study.

Bi-weekly combination of gemcitabine and oxaliplatin has proven active and tolerable and warrants further study. In addition, fixed dose rate infusion of gemcitabine has shown interesting as the ability of mononuclear cells to accumulate gemcitabine triphosphate during therapy seems to be saturable.

We propose a phase I-II study of a bi-weekly schedule of gemcitabine, oxaliplatin and capecitabine. This regimen could be feasible in an out-patients setting.

The phase I part is a standard dose escalation study for patients with solid tumors. In the phase II part the recommended dose is studied in patients with advanced cholangiocarcinoma.


Condition Intervention Phase
Cholangiocarcinoma
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Capecitabine
Phase 1
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 I-II Study of bi-Weekly Fixed Dose Rate Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • Response

Secondary Outcome Measures:
  • Safety
  • Time to progression
  • SUrvival

Estimated Enrollment: 39
Study Start Date: June 2004
Study Completion Date: February 2008
Detailed Description:

Design

Open, non-randomized phase I/II study.

Purpose:

Phase I part To find MTD and RFTD for the combination of gemcitabine, oxaliplatin and capecitabine.

Dose Escalating Schedule Dose level Dose Gemcitabine 10 mg/m2/min 600-1000 mg/m2 day 1 and 14 Capecitabine p.o. x 2 daily. 1000-1250 mg/m2 day 1-7 and 14-21 Oxaliplatin 60-80 mg/m2day 1 and 14 Drugs: G C O Level 1 600 1000 60 Level 2 800 1000 60 Level 3 1000 1000 60 Level 4 1000 1250 60 Level 5 1000 1250 80 Level 6 1200 1250 80 Start level: Level 1, 3 patients per level

Phase II part The primary endpoint is the objective response rate The secondary endpoint is toxicity, response duration and time to progression.

Treatment:

Gemcitabine Gemcitabine is given intravenously on day 1 and 14 with a fixed dose rate of 10 mg/m2/min.

Oxaliplatin Oxaliplatin is given intravenously on day 1 and 14 as a 2 hours infusion.

Capecitabine Capecitabine is given orally and administered in tablets of 150 mg and 500 mg. The dose is administered twice daily with 12 hours interval, in the morning and evening during or latest 30 minutes after a meal.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven intra- or extrahepatic cholangiocarcinoma, papilla of the Vater or gallbladder carcinoma.
  • PS 0-2
  • Age 18-75
  • Life expectancy > 12 weeks
  • Normal bone marrow function (neutrophiles > 1,5 x 109/l and platelets > 100 x 109/l)
  • Bilirubin < 1,5 x UNL
  • Transaminases < 3 x UNL
  • Normal renal function, Cr-EDTA clearance > 50 ml/min
  • No chemotherapy, radiotherapy or immunotherapy 4 weeks prior to inclusion
  • No known DPD-deficiency
  • No neuropathy
  • No uncontrolled, severe concurrent medical disease
  • Signed informed consent

Exclusion Criteria:

  • Chemotherapy, radiotherapy or immunotherapy 4 weeks prior to inclusion
  • Experimental therapy < 8 weeks prior to inclusion
  • Uncontrolled, severe concurrent medical disease
  • Prior malignancy during the last 5 years, except for non-melanoma skin cancer and carcinoma in situ cervix uteri.
  • Allergy to gemcitabine, oxaliplatin or capecitabine
  • Pregnancy or lactation
  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: NCT00350961

Locations
Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Vejle Sygehus
Vejle, Denmark, 7100
Sponsors and Collaborators
Rigshospitalet, Denmark
Henrik Jensen, Dept. of Oncology, Vejle Sygehus, Vejle, Denmark
Investigators
Principal Investigator: Ulrik Lassen, MD., PH.D. Rigshospitalet, Dept. of Oncology
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00350961     History of Changes
Other Study ID Numbers: GEMOXEL cholangiocarcinoma
Study First Received: July 10, 2006
Last Updated: August 25, 2008
Health Authority: Denmark: Danish Medicines Agency

Keywords provided by Rigshospitalet, Denmark:
Cholangiocarcinoma
Fixed dose rate
Gemcitabine
Oxaliplatin
Capecitabine

Additional relevant MeSH terms:
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Capecitabine
Fluorouracil
Oxaliplatin
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 August 21, 2014