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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01692704
Recruitment Status : Completed
First Posted : September 25, 2012
Last Update Posted : March 25, 2016
Information provided by (Responsible Party):
University of Zurich

Brief 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

Condition or disease Intervention/treatment Phase
Cholangiocellular Carcinoma Drug: Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : April 2012
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01692704

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University Hospital Zurich, Department of Oncology
Zurich, ZH, Switzerland, 8091
Sponsors and Collaborators
University of Zurich
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Principal Investigator: Panagiotis Samaras, MD University Hospital Zurich, Department of Oncology
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Responsible Party: University of Zurich Identifier: NCT01692704    
Other Study ID Numbers: ONK-USZ-003
First Posted: September 25, 2012    Key Record Dates
Last Update Posted: March 25, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs