Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

NCT ID: NCT00350961

Last Updated: 2008-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2008-02-29

Brief Summary

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.

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.

Conditions

Cholangiocarcinoma

Keywords

Cholangiocarcinoma; Fixed dose rate; Gemcitabine; Oxaliplatin; Capecitabine

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Gemcitabine

Intervention Type: DRUG

Oxaliplatin

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henrik Jensen, Dept. of Oncology, Vejle Sygehus, Vejle, Denmark

UNKNOWN

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Principal Investigators

Ulrik Lassen, MD., PH.D.

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Dept. of Oncology

Locations

Rigshospitalet

Copenhagen, , Denmark

Vejle Sygehus

Vejle, , Denmark

Countries

Denmark

Other Identifiers

GEMOXEL cholangiocarcinoma

Identifier Type: -

Identifier Source: org_study_id