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

NCT ID: NCT01692704

Last Updated: 2016-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2016-03-31

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

Conditions

Cholangiocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Selective intra-arterial floxuridine and systemic gemcitabine and cisplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Panagiotis Samaras, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Zurich, Department of Oncology

Locations

University Hospital Zurich, Department of Oncology

Zurich, Canton of Zurich, Switzerland

Countries

Switzerland

Other Identifiers

ONK-USZ-003

Identifier Type: -

Identifier Source: org_study_id