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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Delcath Systems Inc.
ClinicalTrials.gov Identifier:
NCT00096083
First received: November 9, 2004
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Cancer
Drug: isolated perfusion
Drug: melphalan
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Delcath Systems Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the patterns of recurrence following percutaneous hepatic perfusions (PHP) with melphalan [ Time Frame: Survival ] [ Designated as safety issue: No ]
  • To determine the progression free and overall survival in patients with hepatic malignancies following this therapy [ Time Frame: Survivial ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: September 2004
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Melphalan Administration PHP Drug: isolated perfusion Drug: melphalan

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 16 and over

Sex

  • Male or Female

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

  • 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

Renal

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

Cardiovascular

  • No congestive heart failure
  • LVEF ≥ 40%

Pulmonary

  • No chronic obstructive pulmonary disease
  • FEV_1 ≥ 30% of predicted
  • DLCO ≥ 40% of predicted

Immunologic

  • 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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 1 month since prior biologic therapy and recovered

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • No prior Whipple resection

Other

  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096083

Locations
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.
Investigators
Principal Investigator: Marybeth Hughes, MD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: Delcath Systems Inc.
ClinicalTrials.gov Identifier: NCT00096083     History of Changes
Obsolete Identifiers: NCT00091455
Other Study ID Numbers: CDR0000391827, NCI-04-C-0273, NCI-6332, DELCATH-G990039
Study First Received: November 9, 2004
Last Updated: October 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Delcath Systems Inc.:
WDHA syndrome
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

Additional relevant MeSH terms:
Melphalan
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014