Brief Title
Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma
Official Title
Phase I-II Study of bi-Weekly Fixed Dose Rate Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Response
Secondary Outcome
Safety
Condition
Cholangiocarcinoma
Intervention
Gemcitabine
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
39
Start Date
June 2004
Completion Date
February 2008
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
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Ulrik Lassen, MD., PH.D., ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT00350961
Organization ID
GEMOXEL cholangiocarcinoma
Study Sponsor
Rigshospitalet, Denmark
Collaborators
Henrik Jensen, Dept. of Oncology, Vejle Sygehus, Vejle, Denmark
Study Sponsor
Ulrik Lassen, MD., PH.D., Principal Investigator, Rigshospitalet, Dept. of Oncology
Verification Date
August 2008