Patient case: 50-year-old male with cholangiocarcinoma; genetic feature: IDH1

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

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: 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

Relevance to patient case: not relevant