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Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), July 2009
First Received: November 9, 2004   Last Updated: September 17, 2009   History of Changes
Sponsor: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00096083
  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 II

Study Type: Interventional
Study Design: Treatment, Open Label
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patterns of recurrence [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: September 2004
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
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
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 Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
Sponsors and Collaborators
Investigators
Principal Investigator: Marybeth S. Hughes, MD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000391827, NCI-04-C-0273, NCI-6332, DELCATH-G990039
Study First Received: November 9, 2004
Last Updated: September 17, 2009
ClinicalTrials.gov Identifier: NCT00096083     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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:
Melphalan
Liver Diseases
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Liver Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on November 27, 2009