Downsizing of Unresectable Cholangiocarcinoma by Combined Intravenous and Intra-arterial Chemotherapy
An open label, prospective, non-randomized single arm study. Combination of two treatment modalities - HAI with FUDR and systemic chemotherapy with cisplatin and gemcitabine.
Definition of the maximum tolerated dose (MTD) of intravenous gemcitabine in combination with intravenous cisplatin and intra-arterial FUDR. Definition of safety and toxicity of this combined regional and systemic treatment approach. Definition of the response rate after 3 months of hepatic intra-arterial chemotherapy with continuous infusion FUDR with or without ligation of the right or left portal vein, in combination with 3 months of systemic cisplatin and gemcitabine in patients with unresectable intrahepatic or hilar CCC.
A total of 9-18 patients are required. 3-6 patients per dose level. A maximum of three dose levels (1 - 3) has been defined.
Statistical Methodology: Traditional 3+3 dosing algorithm to find MTD.
- Trial with medicinal product
|Cholangiocellular Carcinoma||Drug: Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Downstaging of Unresectable Intrahepatic or Hilar Cholangiocellular Carcinoma by Selective Intra-arterial Floxuridine and Systemic Cisplatin and Gemcitabine. A Dose Finding Single Center Phase IIa Study|
- Dose limiting toxicities (DLT) of intravenous gemcitabine with concomitant administration of FUDR-HAI and intravenous cisplatin. [ Time Frame: 6 weeks ]Dose limiting toxicities will be assessed to define the maximum tolerated dose (MTD) of gemcitabine in combination with fixed doses of cisplatin and FUDR. DLTs are per protocol prespecified AE or laboratory abnormalities observed during the first 6 weeks of study treatment. The MTD is one dose level below the dose level that caused DLTs in ≥ one third of patients (2 or more in a cohort of 6 patients), as determined by a traditional 3+3 algorithm.
|Study Start Date:||April 2012|
|Study Completion Date:||March 2016|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: HAI with FUDR & systemic cisplatin and gemcitabin
FUDR: 0.2mg/kg/day continuously i.a. for 14 days Cisplatin: 25mg/m2 i.v. Gemcitabin: different doses according to dose level 600, 800, or 1000 mg/m2 i.v.
Drug: Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin
Intra-arterial floxuridine:0.2 mg/KG/day for 14 days, repeated day 29. Overall 3 applications.
Systemic cisplatin: 25 mg/m2 at days 1 and 8, repeated day 22. Overall 8 applications.
Systemic gemcitabine: Three different dose levels will be tested; 600 mg/m2, 800 mg/m2, or 1000 mg/m2, at days 1 and 8, repeated day 22. Overall 8 applications.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01692704
|University Hospital Zurich, Department of Oncology|
|Zurich, ZH, Switzerland, 8091|
|Principal Investigator:||Panagiotis Samaras, MD||University Hospital Zurich, Department of Oncology|