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

Cholangiocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01692704
• Other study ID #: ONK-USZ-003
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 6, 2012
• Last updated: March 24, 2016
• Start date: April 2012
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Cholangiocellular Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, Department of Oncology	Zurich	ZH

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLT) of intravenous gemcitabine with concomitant administration of FUDR-HAI and intravenous cisplatin.	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.	6 weeks	Yes