Back to results

A Phase II Study of Continuous Hepatic Arterial Infusion With Floxuridine (FUDR) and Dexamethasone (DEX) in Patients With Unresectable Primary Hepatic Malignancy

Primary Purpose

Hepatic Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

FLOXURIDINE

About this trial

This is an interventional treatment trial for Hepatic Cancer focused on measuring FUDR, FLOXORUIDINE, DEXAMETHASONE, Hepatic, Cancer, 02-120

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with a liver mass that is radiographically consistent with HCC and a serum alpha fetoprotein (AFP) > 500 ng/dl do not require biopsy confirmation of the diagnosis.
Patients with HCC or ICC undergoing exploration for a possible curative resection but found to have unresectable disease confined to the liver will be eligible, provided that no intraoperative findings would exclude them and prior informed consent has been obtained (see below).
There must be <70% liver involvement by cancer, and the disease must be considered unresectable.
Patients who have failed ablative therapy will be eligible.
Patients must have a KPS > 60% and be considered candidates for general anesthesia and hepatic artery pump placement.
Patients with chronic hepatitis and/or cirrhosis are eligible
Serum albumin must be >2.5 g/dl and total serum bilirubin must be <1.8 mg/dl based on preoperative laboratory values within 14 days of registration.
WBC must be >3500 cells/mm3 and platelet count must be >100,000/mm3 based on preoperative laboratory values within 14 days of registration.
The international normalized ratio (INR) must be less than 1.5 in patients not on coumadin therapy, based on preoperative laboratory values within 14 days of registration.
Age >_ 18 years.
Female patients cannot be pregnant or lactating.
Patients must be able to understand and sign informed consent.

Exclusion Criteria:

Patients who have received prior treatment with FUDR
Patients who have had prior external beam radiation therapy to the liver.
Patients who have a diagnosis of sclerosing cholangitis.
Patients who have a diagnosis of Gilbert's disease.
Patients who have clinical ascites
Patients with hepatic encephalopathy
Patients who have radiographic evidence of esophageal varices or history of variceal hemorrhage.
Patients with occlusion of the main portal vein nor of the right and left portal branches Patients that have concurrent malignancies (except localized basal cell or squamous cell skin cancers). Patient with active infection. Female patients who are pregnant or lactating.

Sites / Locations

Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Treatment Response

To assess the efficacy of continuous arterial infusion (HAI) of FUDR (Floxuridine) and dexamethasone (DEX) in patients with unresectable hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Number of Patients With Treatment Related Toxicity

Toxicity evaluated and graded according to the National Cancer Institute, CTCAE v4.0

Secondary Outcome Measures

Disease Progression

Median Survival

Median Survival from Initiation of Hepatic Arterial Infusion

Full Information

NCT ID

NCT00587067

First Posted

December 21, 2007

Last Updated

March 31, 2023

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Wake Forest University

1. Study Identification

Unique Protocol Identification Number

NCT00587067

Brief Title

A Phase II Study of Continuous Hepatic Arterial Infusion With Floxuridine (FUDR) and Dexamethasone (DEX) in Patients With Unresectable Primary Hepatic Malignancy

Official Title

A Phase II Study of Continuous Hepatic Arterial Infusion With Floxuridine (FUDR) and Dexamethasone (DEX) in Patients With Unresectable Primary Hepatic Malignancy

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

June 2003 (undefined)

Primary Completion Date

May 19, 2016 (Actual)

Study Completion Date

May 19, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Wake Forest University

4. Oversight

5. Study Description

Brief Summary

Detailed Description

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 toxicity. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Cancer

Keywords

FUDR, FLOXORUIDINE, DEXAMETHASONE, Hepatic, Cancer, 02-120

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

FLOXURIDINE

Other Intervention Name(s)

FUDR

Intervention Description

[0.16* mg/kg/day X 30 ml] / pump flow rate * If the patient is >25% above ideal body weight, the dose of FUDR will be calculated from an average of the patients actual and ideal body weights. For example, for a patient who is 5ft. 10 inches and weighs 100kg: Ideal Body Weight (kg) = 50 + (2.3 X height in inches over 5 feet) = 50 + (2.3 X 10) = 73 Weight Used for dose calculation = (100 + 73)/2 = 86.5 Therefore, FUDR Dose will be = (0.16 X 86.5 X 30)/Flow Rate If no dose modification due to toxicity is required, the dosages given above (adjusted for changes in weight and pump flow rate) will be repeated on Day 1 of Week 1 of Cycle 2 and all subsequent cycles.

Primary Outcome Measure Information:

Title

Treatment Response

Description

Time Frame

Up to 5 years

Title

Number of Patients With Treatment Related Toxicity

Description

Toxicity evaluated and graded according to the National Cancer Institute, CTCAE v4.0

Time Frame

Up to 5 years

Secondary Outcome Measure Information:

Title

Disease Progression

Time Frame

Up to 5 years

Title

Median Survival

Description

Median Survival from Initiation of Hepatic Arterial Infusion

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with a liver mass that is radiographically consistent with HCC and a serum alpha fetoprotein (AFP) > 500 ng/dl do not require biopsy confirmation of the diagnosis. Patients with HCC or ICC undergoing exploration for a possible curative resection but found to have unresectable disease confined to the liver will be eligible, provided that no intraoperative findings would exclude them and prior informed consent has been obtained (see below). There must be <70% liver involvement by cancer, and the disease must be considered unresectable. Patients who have failed ablative therapy will be eligible. Patients must have a KPS > 60% and be considered candidates for general anesthesia and hepatic artery pump placement. Patients with chronic hepatitis and/or cirrhosis are eligible Serum albumin must be >2.5 g/dl and total serum bilirubin must be <1.8 mg/dl based on preoperative laboratory values within 14 days of registration. WBC must be >3500 cells/mm3 and platelet count must be >100,000/mm3 based on preoperative laboratory values within 14 days of registration. The international normalized ratio (INR) must be less than 1.5 in patients not on coumadin therapy, based on preoperative laboratory values within 14 days of registration. Age >_ 18 years. Female patients cannot be pregnant or lactating. Patients must be able to understand and sign informed consent. Exclusion Criteria: Patients who have received prior treatment with FUDR Patients who have had prior external beam radiation therapy to the liver. Patients who have a diagnosis of sclerosing cholangitis. Patients who have a diagnosis of Gilbert's disease. Patients who have clinical ascites Patients with hepatic encephalopathy Patients who have radiographic evidence of esophageal varices or history of variceal hemorrhage. Patients with occlusion of the main portal vein nor of the right and left portal branches Patients that have concurrent malignancies (except localized basal cell or squamous cell skin cancers). Patient with active infection. Female patients who are pregnant or lactating.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William Jarnagin, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mskcc.org/mskcc/html/44.cfm

Description

Memorial Sloan-Kettering Cancer Center

Learn more about this trial

A Phase II Study of Continuous Hepatic Arterial Infusion With Floxuridine (FUDR) and Dexamethasone (DEX) in Patients With Unresectable Primary Hepatic Malignancy

We'll reach out to this number within 24 hrs