Protocol Number: 04-C-0263

Title:

A Phase I Dose Escalation Study of Heat Activated Liposome Delivery of Doxorubicin and Radiofrequency Ablation of Primary and Metastatic Tumors of the Liver

Number:

04-C-0263

Summary:

This study will evaluate the safety and side effects of combining chemotherapy using a heat activated liposme carrying doxorubicin with radiofrequency ablation (RFA) in patients with liver cancer that cannot be treated with standard surgery. Doxorubicin is an anti-cancer drug that, in this study, is given in a formulation called Thermodox. The drug is contained in a tiny fat bubble called a liposome that is specially designed to release the drug when heated. RFA is a procedure that uses a special needle device with "points" that kill tumor cells with heat. Heating the tumor during RFA causes doxorubicin to be released directly into the tumor, killing any cancer cells that were not destroyed by the RFA.

Patients 18 years of age and older who have inoperable liver cancer may be eligible for this study. Candidates are screened with a medical history, physical examination, blood tests, electrocardiogram (EKG), and computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) scans. These tests are repeated at various intervals during the study to monitor disease progress.

CT is an x-ray test that provides detailed pictures of the inside of the body. The patient lies on a table that moves into the middle of a large, donut-shaped scanner. The scanner can move around the body to take pictures at different angles, which are viewed on a computer monitor. PET can be used to detect tumors and may be useful for determining the extent of disease and response to treatment. The patient is given an injection of a glucose (sugar) solution called fluorodeoxyglucose (FDG) in which a radioactive "tracer" has been attached to the glucose molecule. A special camera detects the radiation emitted by the FDG, and the resulting images show how much glucose is being used by the cells. Because rapidly growing cells, such as cancer cells, take up and use more glucose than normal cells do, this test can show tumor activity. MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the patient lies on a table that is moved into the scanner (a narrow cylinder), wearing earplugs to muffle loud knocking sounds that occur during the scanning process. During some of the scan, patients may be asked to hold their breath. Flow studies of the tumor blood vessels may also be obtained with an EKG or a finger probe.

Participants receive Thermodox, infused over 30 minutes through a catheter (thin plastic tube) placed in a vein. The first group of patients entering the study receives the lowest dose of Thermodox; subsequent groups receive increasingly higher doses as long as the side effects remain tolerable and until a maximum dose is reached. Other medicines, including dexamethasone, ranitidine, and benadryl, are given before the Thermodox dose to prevent some side effects and allergic reactions to the drug.

About 15 minutes after the Thermodox is started, the RFA needle is placed in the liver tumors in one of three ways: through the skin (percutaneously); through a tube placed in a small hole cut in the abdomen (laparoscopy); or through an open incision during surgery. The needle points are heated to a high temperature for about 5 minutes to destroy the tumor cells. The total time of the RFA procedure averages from 12 to 60 minutes, depending on the number and size of tumors.

Patients remain in the hospital for about 48 hours and are monitored with frequent blood and urine tests. After discharge, they have blood drawn weekly and they return to NIH after 4 weeks for tumor evaluation with scans, X-rays, and blood tests. The scans and blood tests are repeated every 3 months for the first year and then every 6 months for a total of 3 years, or until the tumors begin to grow.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Maximum Tolerated Dose

Pharmacokinetics

Clinical Response

Doxorubicin

Pharmacodynamics

Tumor Vascular Density

Thermal

Cautery

Liposomes

Recruitment Keyword(s):

None

Condition(s):

Liver Cancer

Metastases

Investigational Drug(s):

Thermodox

Investigational Device(s):

None

Interventions:

Drug: Thermodox

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Siperstein AE, Rogers SJ, Hansen PD, Gitomirsky A. Laparoscopic thermal ablation of hepatic neuroendocrine tumor metastases. Surgery. 1997 Dec;122(6):1147-54; discussion 1154-5.

Buscarini L, Rossi S, Fornari F, Di Stasi M, Buscarini E. Laparoscopic ablation of liver adenoma by radiofrequency electrocauthery. Gastrointest Endosc. 1995 Jan;41(1):68-70.

Livraghi T, Solbiati L, Meloni MF, Gazelle GS, Halpern EF, Goldberg SN. Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology. 2003 Feb;226(2):441-51.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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