Hepatic Arterial Infusion Of Melphalan With Hepatic Perfusion In Treating Patients With Unresectable Liver Cancer

Study Overview

Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer

RATIONALE: Hepatic arterial infusion uses a catheter to deliver anticancer substances directly into the liver. Drugs used in chemotherapy, such as melphalan, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different ways may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving an hepatic arterial infusion of melphalan together with hepatic perfusion works in treating patients with unresectable liver cancer.

OBJECTIVES: Primary * Determine the response rate and duration of response in patients with unresectable primary or metastatic liver cancer treated with intrahepatic arterial infusion of melphalan with venous filtration via peripheral hepatic perfusion. Secondary * Determine the patterns of recurrence in patients treated with this regimen. * Determine progression-free and overall survival of patients treated with this regimen. * Evaluate the safety and tolerability of this regimen in these patients. * Assess the filter characteristics including melphalan pharmacokinetics and filtration of cytokines and clotting factors during and after treatment. OUTLINE: Patients are stratified according to primary tumor histology (neuroendocrine tumor vs primary hepatic malignancy vs adenocarcinoma of gastrointestinal or other origin). Patients undergo peripheral isolated hepatic perfusion in which a catheter is placed via the groin into the hepatic artery and another into the hepatic vein. Patients then receive melphalan as an intrahepatic arterial infusion over 15-30 minutes. Treatment repeats approximately every 3-8 weeks for up to 6 total infusions in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 4 months for 1 year, and then periodically thereafter. PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study within 4-5 years.

Cancer

DRUG: isolated perfusion
DRUG: melphalan

CDR0000391827
NCI-04-C-0273
NCI-6332
DELCATH-G990039

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2004-11-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-10-22
First Submitted that Met QC Criteria 2004-11-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-10-23
First Posted (ESTIMATED) 2004-11-09	Results First Posted N/A	Last Verified 2013-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Melphalan Administration PHP	DRUG: isolated perfusion DRUG: melphalan

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Melphalan Administration PHP

DRUG: isolated perfusion

DRUG: melphalan

Primary Outcome Measures	Measure Description	Time Frame
To determine the response rate and duration of response to intra-hepatic infusion of melphalan with subsequent venous hemofiltration in patients with primary and metastatic hepatic malignancies		Survivial

Secondary Outcome Measures	Measure Description	Time Frame
To determine the patterns of recurrence following percutaneous hepatic perfusions (PHP) with melphalan		Survival
To determine the progression free and overall survival in patients with hepatic malignancies following this therapy		Survivial

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
16 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed hepatic malignancy

Unresectable disease
Disease predominantly in the parenchyma of the liver
One of the following primary tumor histologies:

Adenocarcinoma of gastrointestinal or other origin
Neuroendocrine tumor (except gastrinoma)
Primary hepatic malignancy (e.g., hepatocellular cancer or intra-hepatic cholangiocarcinoma)
Cutaneous or ocular melanoma (patients must have received prior regional melphalan therapy)
Hepatic metastases from colorectal tumors allowed provided patient has undergone prior first-line chemotherapy, including irinotecan or oxaliplatin
Limited unresectable extrahepatic disease on preoperative radiological studies allowed if life-limiting component of progressive disease is in the liver

Limited extrahepatic disease includes, but is not limited to, the following:

Up to 4 pulmonary nodules each < 1 cm in diameter
Retroperitoneal lymph nodes each < 3 cm in diameter
Less than 10 skin or subcutaneous metastases each < 1 cm in diameter
Asymptomatic bone metastases that have been or could be palliatively treated with external beam radiotherapy
Resectable solitary metastasis to any site
Hormone receptor status:

Not specified

16 and over

Male or Female

Not specified

ECOG 0-2

Not specified

Platelet count ≥ 75,000/mm^3
Hematocrit > 27%
Absolute neutrophil count ≥ 1,300/mm^3

Bilirubin ≤ 2.0 mg/dL
PT ≤ 2 seconds of upper limit of normal (ULN)
AST and ALT ≤ 10 times ULN
No Childs class B or C cirrhosis
No portal hypertension by history, endoscopy, or radiologic studies

Creatinine ≤ 1.5 mg/dL OR
Creatinine clearance > 60 mL/min

No congestive heart failure
LVEF ≥ 40%

No chronic obstructive pulmonary disease
FEV\_1 ≥ 30% of predicted
DLCO ≥ 40% of predicted

No active infection
No severe allergic reaction to iodine contrast agent that is not controlled by premedication with antihistamines or steroids
No known hypersensitivity reaction to melphalan or heparin in the presence of a heparin induced thrombocytopenia (HIT) antibody

Weight > 35 kg
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No documented latex allergy
No evidence of intracranial abnormalities which would lead to risk for bleeding with anticoagulation (e.g., stroke or active metastasis)
No evidence of active ulcer disease

More than 1 month since prior biologic therapy and recovered

See Disease Characteristics
More than 1 month since prior chemotherapy and recovered

Premenopausal women (i.e., have had a period within the past 12 months) must be willing to undergo hormonal suppression during study treatment

See Disease Characteristics
More than 1 month since prior radiotherapy and recovered

No prior Whipple resection

Prior intrahepatic perfusion (with or without arterial infusion with floxuridine) or peripheral hepatic perfusion allowed provided the patient had a radiographic partial response of 3 months' duration after therapy
No concurrent immunosuppressive drugs
No concurrent chronic anticoagulation therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Marybeth Hughes, MD, NCI - Surgery Branch

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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Clinical Trial Record