A Phase II Study of Continuous Hepatic Arterial Infusion With Floxuridine (FUDR) and Dexamethasone (DEX) in Patients With Unresectable Primary Hepatic Malignancy
This phase II study aims to evaluate regional chemotherapy in patients with unresectable
primary hepatic malignancy. Specifically, eligible patients with hepatocellular carcinoma
and peripheral cholangiocarcinoma, considered unresectable after review by the Hepatobiliary
Surgery service, will undergo hepatic artery pump placement and continuous infusion of FUDR.
The protocol includes radiological and biological correlative studies.
The primary objectives of the study are 1.) to assess the efficacy of continuous hepatic
arterial infusion (HAI) of FUDR and dexamethasone (DEX) in patients with unresectable
hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and 2.)to assess
patient tolerability of this therapy stratified by degree of underlying hepatic parenchymal
disease, as determined on liver biopsy. Secondary objectives are 1.) to use dynamic MRI to
evaluate changes in tumor perfusion during treatment and to correlate these findings with
radiographic tumor response and 2.) to investigate molecular genetic changes associated with
these tumors using comparative genomic hybridization and cDNA array from tumor and liver
biopsy specimens obtained at the time of operation. All patients enrolled in the study will
begin HAI FUDR at 0.16 mg/kg/day. An initial cohort of 12 patients will be enrolled and
treated. Dose limiting toxicity (DLT) related to FUDR is defined by changes in liver
function blood tests that are unrelated to disease progression or mechanical biliary
obstruction. Modifications in the FUDR dose may be required. A patient will be considered
intolerant of therapy if treatment must be stopped due to DLT at least once during the first
3 months. Treatment will continue as long as there is at least stable disease and acceptable
If, in the initial cohort, 4 or more patients (> 30%) are intolerant of therapy or if there
are not at least 2 responders, then the study will be terminated. Otherwise, accrual will
continue to a maximum of 35 patients.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the efficacy of continuous arterial infusion (HAI) of FUDR and dexamethasone (DEX) in patients with unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
William Jarnagin, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
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