We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00096083
Recruitment Status : Completed
First Posted : November 9, 2004
Last Update Posted : October 23, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Delcath Systems Inc.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Cancer Drug: isolated perfusion Drug: melphalan Phase 2

Detailed Description:



  • 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.


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Of Hepatic Arterial Infusion Of Melphalan With Venous Filtration Via Peripheral Hepatic Perfusion (PHP) For Unresectable Primary And Metastatic Cancers Of The Liver
Study Start Date : September 2004
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2012

Arm Intervention/treatment
Active Comparator: Melphalan Administration PHP Drug: isolated perfusion
Drug: melphalan

Primary Outcome Measures :
  1. 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 [ Time Frame: Survivial ]

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • 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


Biologic therapy

  • More than 1 month since prior biologic therapy and recovered


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

Endocrine therapy

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00096083

Layout table for location information
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Delcath Systems Inc.
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Marybeth Hughes, MD NCI - Surgery Branch
Layout table for additonal information
Responsible Party: Delcath Systems Inc.
ClinicalTrials.gov Identifier: NCT00096083    
Obsolete Identifiers: NCT00091455
Other Study ID Numbers: CDR0000391827
First Posted: November 9, 2004    Key Record Dates
Last Update Posted: October 23, 2013
Last Verified: October 2013
Keywords provided by Delcath Systems Inc.:
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
liver metastases
adenocarcinoma of the colon
adenocarcinoma of the esophagus
adenocarcinoma of the extrahepatic bile duct
adenocarcinoma of the gallbladder
adenocarcinoma of the pancreas
adenocarcinoma of the rectum
adenocarcinoma of the stomach
carcinoma of the appendix
recurrent gallbladder cancer
unresectable gallbladder cancer
recurrent colon cancer
stage IV colon cancer
recurrent esophageal cancer
stage IV esophageal cancer
recurrent extrahepatic bile duct cancer
unresectable extrahepatic bile duct cancer
recurrent gastric cancer
stage IV gastric cancer
recurrent rectal cancer
stage IV rectal cancer
small intestine adenocarcinoma
recurrent small intestine cancer
recurrent islet cell carcinoma
recurrent pheochromocytoma
metastatic pheochromocytoma
pulmonary carcinoid tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs