Isolated Hepatic Perfusion With Melphalan in Treating Patients With Primary Unresectable Liver Cancer or Liver Metastases

A Phase II Study of Isolated Hepatic Perfusion (IHP) With Melphalan for Metastatic Unresectable Cancers of the Liver

RATIONALE: Drugs used in chemotherapy use 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 isolated hepatic perfusion with melphalan works in treating patients with primary unresectable liver cancer or liver metastases.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer; Liver Cancer; Neuroendocrine Carcinoma; Islet Cell Tumor
• Intervention / Treatment: Procedure: conventional surgery; Drug: melphalan; Drug: isolated perfusion

Detailed Description

OBJECTIVES:

• Determine response rate, duration of response, and patterns of recurrence in patients with primary or metastatic, unresectable cancers of the liver after treatment with isolated hepatic perfusion with melphalan.
• Determine the disease-free and overall survival of patients treated with this regimen.

OUTLINE: Patients who are otherwise eligible undergo an exploratory laparotomy of the peritoneal cavity. Patients with peritoneal seeding, unresectable extrahepatic metastases, or unresectable pathologically-involved lymph nodes outside area of portahepatis do not receive treatment. Remaining patients receive isolated hepatic perfusion with melphalan. Liver perfusion proceeds for 1 hour.

Patients are followed at 6 weeks, every 3 months for 2 years, and then every 4 months until disease progression.

PROJECTED ACCRUAL: A maximum of 67 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven liver cancer meeting 1 of the following criteria:

  • Primary unresectable hepatocellular or cholangiocellular carcinoma

  • Metastatic cancer to the liver originating from one of the following:

    • Intraocular melanoma (closed to accrual as of 10/17/03)
    • Islet cell carcinoma

    • Adenocarcinoma of the colon or rectum limited to parenchyma of the liver

      • No evidence of other unresectable extrahepatic colorectal metastasis
  • Other neuroendocrine tumors, such as carcinoid tumors
• Measurable disease

PATIENT CHARACTERISTICS:

Age:

• Any age

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count greater than 100,000/mm^3
• Hematocrit greater than 27.0%
• WBC at least 2,500/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)
• PT no greater than 2 seconds above upper limit of normal
• Elevated SGOT and SGPT allowed if not due to hepatitis
• No biopsy-proven cirrhosis or evidence of significant portal hypertension
• No prior or concurrent veno-occlusive disease
• Patients with positive hepatitis B or C surface antigen serology and chronic active hepatitis are eligible provided there is no evidence of cirrhosis

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Congestive heart failure allowed if LVEF ≥ 40%

Pulmonary:

• No chronic obstructive pulmonary disease or other chronic pulmonary disease with pulmonary function tests less than 50% predicted for age

Other:

• Weight greater than 30 kg
• Not pregnant or nursing
• Negative pregnancy test
• No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 1 month since prior anticancer biologic therapy and recovered

Chemotherapy:

• At least 1 month since prior anticancer chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 1 month since prior anticancer radiotherapy and recovered

Surgery:

• Not specified

Other:

• Prior intrahepatic arterial infusion therapy allowed
• No chronic use of anticoagulants
• No concurrent immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate
Overall survival
Duration of response
Disease-free survival
Patterns of recurrence

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Feldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, Steinberg SM, Liewehr DJ, Kleiner DE, Alexander HR. Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy. J Clin Oncol. 2003 Dec 15;21(24):4560-7. doi: 10.1200/JCO.2003.04.150.

Study record dates

Study Major Dates

• Study Start: August 1, 1999
• Study Completion (ACTUAL): January 1, 2006

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): March 23, 2012
• Last Update Submitted That Met QC Criteria: March 21, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer; liver metastases; advanced adult primary liver cancer; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma; stage IV childhood liver cancer; recurrent childhood liver cancer; recurrent islet cell carcinoma; childhood hepatocellular carcinoma; stage III childhood liver cancer; neuroendocrine carcinoma; adult primary cholangiocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Liver Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Neuroendocrine Tumors; Adenoma; Pancreatic Neoplasms; Carcinoma; Liver Neoplasms; Carcinoma, Neuroendocrine; Adenoma, Islet Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: 990123; 99-C-0123; CDR0000067220