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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. 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.

Tracking Information
First Submitted Date  ICMJE November 9, 2004
First Posted Date  ICMJE November 9, 2004
Last Update Posted Date October 23, 2013
Study Start Date  ICMJE September 2004
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2012)
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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2012)
  • To determine the patterns of recurrence following percutaneous hepatic perfusions (PHP) with melphalan [ Time Frame: Survival ]
  • To determine the progression free and overall survival in patients with hepatic malignancies following this therapy [ Time Frame: Survivial ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: isolated perfusion
  • Drug: melphalan
Study Arms  ICMJE Active Comparator: Melphalan Administration PHP
  • Drug: isolated perfusion
  • Drug: melphalan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 22, 2013)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00096083
Other Study ID Numbers  ICMJE CDR0000391827
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Delcath Systems Inc.
Study Sponsor  ICMJE Delcath Systems Inc.
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Marybeth Hughes, MD NCI - Surgery Branch
PRS Account Delcath Systems Inc.
Verification Date October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP