Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

Rigshospitalet

Status and phase

Completed

Phase 2

Phase 1

Conditions

Cholangiocarcinoma

Treatments

Drug: Oxaliplatin

Drug: Capecitabine

Drug: Gemcitabine

Study type

Interventional

Funder types

Other

Identifiers

NCT00350961

GEMOXEL cholangiocarcinoma

Details and patient eligibility

About

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.

Full 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.

Enrollment

39 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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