downsizing of unresectable cholangiocarcinoma by combined intravenous and intra-arterial chemotherapy

Conditions: Cholangiocellular Carcinoma

Summary: 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


Eligibility criteria:
inclusion criteria: * histologically or cytologically proven cholangiocellular carcinoma including gallbladder cancer. * non-resectable cholangiocellular carcinoma as judged within an interdisciplinary tumor-board including senior hepatobiliary surgeons. non- resectability is based on insufficient remnant liver volume. * patient is not a candidate for liver transplantation * who performance score 0 or 1 * no extrahepatic tumor, as evaluated by pet/ct scan of the chest and the abdomen/pelvis with the exception of potentially resectable small lung nodules or hilar lymph node involvement. * the assessment is done within 21 days before registration. * adequate liver function or kidney function tests, including any of the following: * bilirubin \< 2 x uln * aspartate-aminotransferase (ast) \< 5 x uln * alanine-aminotransferase (alt) \< 5 x uln * alkaline phosphatase \< 5 x uln * estimated creatinine clearance \> 60 ml/min (using the cockcroft formula) * adequate hematological values: * hemoglobin \> 80 g/l * leucocytes \> 3.00 g/l, * neutrophils \> 1.00 g/ll * platelets \> 100 g/l * signed written informed consent * patient age \>/= 18 years * presentation of the case at the interdisciplinary tumor-board attended by hepatobiliary surgeons, oncologists, hepatologists and radiologists * women who are not breastfeeding and are using effective contraception if sexually active, who are not pregnant and agree not to become pregnant during the 12 months thereafter. a negative pregnancy test before inclusion into the trial is required for women \< 50 years. * men who agree not to father a child during participation in the trial or during the 12 months thereafter. * patient compliance and geographic proximity allow proper staging and follow- up. exclusion criteria: * anatomic variant in arteriogram which prevents selective delivery of the chemotherapy to the liver * life expectancy \< 3 months * severe medical or psychiatric co-morbidity prohibiting the planned treatment or the giving of informed consent * any man or woman of childbearing age in case of inadequate contraception * pregnancy or breastfeeding woman * known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. * treatment in clinical trial within 30 days prior to trial entry. * active heart disease defined as congestive heart failure \> nyha class 2 * past or current history (within the last 2 years prior to treatment start) of other malignancies except basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix * inability or unwillingness to comply with the study protocol