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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00587067
• Collaborator: Wake Forest University (Other)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 155.6
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Cancer	Drug: FLOXURIDINE	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2003
• Actual Primary Completion Date: May 19, 2016
• Actual Study Completion Date: May 19, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1

Drug: FLOXURIDINE; [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.; Other Names: FUDR

Outcome Measures

Primary Outcome Measures

1. Treatment Response [Up to 5 years]

   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).

2. Number of Patients With Treatment Related Toxicity [Up to 5 years]

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

Secondary Outcome Measures

1. Disease Progression [Up to 5 years]

Other Outcome Measures

1. Molecular Genetic Changes Associated With These Tumors [5 years]

   Use comparative genomic hybridization and cDNA array from tumor and liver biopsy specimens obtained at the time of operation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Wake Forest University

Investigators

• Principal Investigator: William Jarnagin, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00587067
• Other Study ID Numbers: 02-120; NCT00310102
• First Posted: Jan 7, 2008
• Last Update Posted: Apr 20, 2021
• Last Verified: May 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: FUDR; FLOXORUIDINE; DEXAMETHASONE; Hepatic; Cancer; 02-120
• Additional relevant MeSH terms: Liver Neoplasms; Floxuridine

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual 6/24/2003, Protocol Closed to Accrual 7/24/2007, Primary Completion Date 5/19/2016, Recruitment location is the medical clinic

Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	FLOXURIDINE: [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.
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	FLOXURIDINE: [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.
Overall Participants	34
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.5
Sex: Female, Male (Count of Participants)
Female	22 64.7%
Male	12 35.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.9%
Not Hispanic or Latino	31 91.2%
Unknown or Not Reported	2 5.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 5.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	30 88.2%
More than one race	0 0%
Unknown or Not Reported	2 5.9%
Region of Enrollment (participants) [Number]
United States	34 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	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 Floxuridine.
Measure Participants	34
Partial Response	16 47.1%
Stable Disease	14 41.2%
Progression of Disease	4 11.8%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	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 Floxuridine.
Measure Participants	34
Number [participants]	34 100%

3. Secondary Outcome

Title	Disease Progression
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	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 Floxuridine.
Measure Participants	34
PD in the liver, alone	18 52.9%
PD in the liver and an extrahepatic location	3 8.8%
PD initially at an extrahepatic site only	12 35.3%
No PD	1 2.9%

4. Other Pre-specified Outcome

Title	Molecular Genetic Changes Associated With These Tumors
Description	Use comparative genomic hybridization and cDNA array from tumor and liver biopsy specimens obtained at the time of operation
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	2 years
Arm/Group Title	Floxuridine + Dexamethasone
Arm/Group Description	FLOXURIDINE: [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.
All Cause Mortality
	Floxuridine + Dexamethasone
	Affected / at Risk (%)	# Events
Total	33/34 (97.1%)
Serious Adverse Events
	Floxuridine + Dexamethasone
	Affected / at Risk (%)	# Events
Total	5/34 (14.7%)
Gastrointestinal disorders
GI, other	1/34 (2.9%)
Melena	1/34 (2.9%)
General disorders
Pain, other	1/34 (2.9%)
Hepatobiliary disorders
Hepatic, other	1/34 (2.9%)
Investigations
Bilirubin Increased	2/34 (5.9%)
Other (Not Including Serious) Adverse Events
	Floxuridine + Dexamethasone
	Affected / at Risk (%)	# Events
Total	5/34 (14.7%)
Cardiac disorders
Supraventricular tachycardia	1/34 (2.9%)
Gastrointestinal disorders
Diarrhea	1/34 (2.9%)
Infections and infestations
Wound infection	3/34 (8.8%)
Investigations
Increased bilirubin	3/34 (8.8%)
Nervous system disorders
Headache/Migraine	1/34 (2.9%)
Psychiatric disorders
Delerium	1/34 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.