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
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Cancer focused on measuring FUDR, FLOXORUIDINE, DEXAMETHASONE, Hepatic, Cancer, 02-120
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.
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
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
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.
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
1
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
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).
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
No
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
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