Downsizing of Unresectable Cholangiocarcinoma by Combined Intravenous and Intra-arterial Chemotherapy

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