Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma

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.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

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