Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma
Condition: Cholangiocarcinoma
MeSH terms: Cholangiocarcinoma
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Gemcitabine; Oxaliplatin; Capecitabine
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Gemcitabine; Capecitabine; Oxaliplatin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cholangiocarcinoma; Fixed dose rate; Gemcitabine; Oxaliplatin; Capecitabine