Protocol Number: 01-C-0215

Title:

A Phase I Study of Hepatic Arterial Infusion of Escalating Dose Melphalan with Venous Filtration for Unresectable Cancers of the Liver

Number:

01-C-0215

Summary:

This study will determine the maximum safe dose and side effects of the drug melphalan given through the DelCath system to treat liver cancer. In this system, the chemotherapy is delivered to the liver through special catheters (flexible plastic tubes) inserted through small puncture holes in the groin area into the blood vessels going into and out of the liver. This allows the drug to be administered directly to the liver in amounts that would not be safe if it circulated throughout the body.

Patients 14 years of age or older with cancer that has arisen in or spread mainly to the liver and cannot be removed surgically may be eligible for this study. Candidates will be screened with a physical examination, blood tests, electrocardiogram (EKG), chest X-ray, and imaging studies, such as X-ray studies, CT scan of the chest, abdomen and pelvis and MRI scan of the liver, to evaluate the tumor. Other tests may be done if medically indicated.

Participants will be admitted to the hospital for treatment under sedation. The groin area is numbed and catheters are placed into the large artery and vein that supply blood to and from the liver, creating a separate circulation for the liver, similar to the heart-lung bypass in open-heart surgery. Once the catheters are in place, melphalan is perfused into the liver for 30 minutes. The circulation to the liver remains separate and the blood is filtered through the DelCath system for another 30 minutes after the drug is given to remove as much of it as possible from the blood coming out of the liver. Following the procedure, patients stay in the intensive care unit for 24 hours for observation.

Patients who enter the study early receive lower doses of melphalan. The dose is increased as the study progresses to determine the highest safe and effective dose. Patients will be informed of the progress of the study at the point they enter. Lower doses may be less effective against the tumor, and higher doses may have a greater risk of side effects.

Patients stay in the hospital for 3 to 5 days during the perfusion part of the study and return to the outpatient clinic after 3 weeks to evaluate recovery. If recovery is satisfactory, a second treatment will be scheduled. About 4 weeks after the second treatment, the tumor will be evaluated to assess the response to therapy. Patients whose tumor has shrunk or stayed the same will be offered another two treatments. When the treatments are finished, patients will return for evaluation every 3 months for 2 years and then every 4 months for a third year. During these visits they will have a physical examination, imaging scans, X-rays and blood tests to evaluate disease status. If the liver tumor grows or spreads beyond the liver during this time, the patient will be taken off the study and other alternatives for care will be discussed.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Histologically or cytologically proven cancer limited to the parenchyma of the liver. Evidence of limited unresectable extrahepatic disease on preoperative radiological studies is acceptable if the life limiting component of progressive disease is in the liver. In patients whose condition makes isolated hepatic perfusion impossible-based on factors such tumor size or location-will be considered for this protocol.

Patients previously treated with IHP with or without hepatic arterial infusion using FUDR will be eligible if they had a bonafide radiographic partial response of 3 months duration to the therapy.

Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their malignancy in the month prior to treatment and must have recovered from all side effects.

Patients must have an ECOG performance standard of less than 3 on the day prior to treatment.

Patients must have adequate hepatic function as evidence by a total serum bilirubin less than or equal to 2.0 mg/dL and a PT within 2 seconds of the upper normal limit.

EXCLUSION CRITERIA:

Patients with biopsy proven cirrhosis with evidence of portal hypertension by history, endoscopy, or radiologic studies will be excluded.

Patients with a history of congestive heart failure with an LVEF less than 40 percent will be excluded.

Patients with COPD or other chronic pulmonary disease with PFT's indicating an FEV1 less than 30 percent or a DLCO less than 40 percent predicted for age will be excluded.

Patients must be 14 years of age or older and greater than 35 kg because of size limitations with respect to percutaneous catheterization of the femoral artery and vein using this system.

Patients must have a platelet count greater than 100,000, a Hct greater than 27.0, an ANC greater than or equal to 1.3 microliter and a creatinine less than or equal to 1.5 mg/dL or a creatinine clearance of greater than 60 mL/min.

Pregnant patients and nursing mothers will be excluded because of the unknown effects of this therapy on the fetus or nursing mothers.

Patients taking immunosuppressive drugs or be on chronic anticoagulation will not be eligible.

Patients with active infections are not eligible.

Patients with severe allergic reactions to iodine contrast which can not be controlled by premedication with antihistamines and steroids are not eligible.

Patients with HIV disease are not eligible.

Patients must be aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks. The patient must be willing to sign an informed consent.

Patients with a known prior hypersensitivity reaction to melphalan will be excluded.

Special Instructions: Currently Not Provided

Keywords:

Maximum Tolerated Dose

Delcath Balloon Catheter

Regional Therapy

Evaluation For Response

Pharmacokinetic Patterns

Recruitment Keywords:

Liver Cancer

Conditions:

Liver Cancer

Investigational Drug(s):

Melphalan

Investigational Device(s):

Delcath Double Balloon Catheter

Contacts:

Geoffrey Seidel, R.N.
National Institutes of Health
Building 10
Room 2B07
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 451-6742
Fax: (301) 402-1788

Electronic Address: seidelg@mail.nih.gov

Citations:

Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma

Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinomaNew dose schedules and survival update

A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases

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