Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma - Full Text View

Sponsors and Collaborators:	Rigshospitalet, Denmark Henrik Jensen, Dept. of Oncology, Vejle Sygehus, Vejle, Denmark
Information provided by:	Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:	NCT00350961

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 I Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Capecitabine Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I-II Study of bi-Weekly Fixed Dose Rate Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

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

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

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

Keywords provided by Rigshospitalet, Denmark:

Cholangiocarcinoma
Fixed dose rate
Gemcitabine
Oxaliplatin
Capecitabine

Study placed in the following topic categories:

Cholangiocarcinoma
Oxaliplatin
Capecitabine
Gemcitabine

Adenocarcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009