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:

Radiofrequency Ablation (RFA) has become an increasingly common modality for the treatment of neoplasms in the liver. A variety of devices are now FDA approved for this indication and a growing body of literature supports this technique as a viable option for patients with primary or metastatic hepatic malignancies. RFA is seen by some as a potential replacement for hepatic resection. However, there are some limitations to the current systems and approaches. The size of lesions that can be treated is limited by the volume of tissue that can be safely ablated by the current generator and needle designs. The current practice is to ablate a 'normal' zone of 1 cm beyond the dimensions of the tumor. Despite this inclusion of a 1 cm zone of normal liver, recurrences at the margins of treated lesions are not uncommon. In order to potentially increase the size of lesions that can be treated, as well as to reduce the rate of local recurrence, we propose the current study. A heat activated liposome carrying doxorubicin will be used as an adjuvant to RFA in order to provide a gradient of chemotherapy surrounding the treated lesion. This phase I trial is designed to determine the safe maximum tolerated dose of systemically delivered heat activated liposome encapsulated doxorubicin administered during a standard RFA treatment of liver lesions. Secondary endpoints will focus on adequacy of ablation and local recurrence.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients will be included who:

Have either primary or metastatic liver lesions who are not candidates for curative surgical resection either due to tumor histology or previous surgery.

Have biopsy proven evidence of cancer with pathology confirmed by the NCI Laboratory of Pathology.

Have less than or equal to 4 lesions and with no single lesion greater than 7cm in maximum diameter.

Have MUGA scan revealing EF greater than or equal to 50%.

Are age greater than or equal to 18 years.

Are willing to return to NIH for their imaging scans.

Are willing to sign informed consent.

Have life expectancy greater than or equal to 3 months.

Have ECOG performance status 0-2.

Patients with non-life-threatening extrahepatic disease in addition to their hepatic metastases are eligible and may receive systemic therapy for their extrahepatic disease if the last dose of any therapy is administered 21 days before enrollment on this study and they have recovered from toxicities to Grade 2 or less.

Patients must agree to no other systemic therapy from the time of study enrollment until they have undergone evaluation on this study (approximately day 28).

EXCLUSION CRITERIA:

Patients will be excluded who:

Are candidates for complete surgical resection.

Have serious medical illnesses including, but not limited to, congestive heart failure, myocardial infarction or cerebral vascular accident within the last six months, life threatening cardiac arrhythmias, acute or chronic liver disease.

Are pregnant or breast-feeding. A negative pregnancy test (urine or serum) is required prior to enrollment.

Have known uncontrollable serious reactions such as anaphylaxis, to the contrast agents used in this study as well as known allergy to egg or egg products.

Have pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices, unless the investigator agrees to not submit the patient to MRI evaluations.

Have PT or PTT greater than 1.5 times control (except in patients who are therapeutically anticoagulated for non-related medical conditions such as atrial fibrillation).

Have platelet count less than 75,000/mm3.

Have total bilirubin greater than 2.0mg/dl.

Have serum creatinine greater than 2.5mg/dl.

Weigh greater than or equal to 136 kg (weight limit for the PET scanner table).

Are on any of the following medications which could have an adverse effect when combined with the study drug, who cannot stop the medication for the duration of the study and 30 days beyond the treatment:

DRUG

Cyclosporine (Sandimmune)

INTERACTION

May induce coma and/or seizures

DRUG

Phenobarbital

INTERACTION

Increases elimination of doxorubicin

DRUG

Phenytoin

INTERACTION

May decrease phenytoin levels

DRUG

Streptozocin ( Zanosar)

INTERACTION

May inhibit the hepatic metabolism

DRUG

Administration of live vaccines in immunosupressed patients

INTERACTION

Hazardous

Have blood glucose of greater than 300 mg/dl or are diagnosed with uncontrollable diabetes.

Special Instructions: Currently Not Provided

Keywords:

Maximum Tolerated Dose

Pharmacokinetics

Clinical Response

Doxorubicin

Pharmacodynamics

Tumor Vascular Density

Thermal

Cautery

Liposomes

Recruitment Keywords:

None

Conditions:

Investigational Drug(s):

Thermodox

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

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.

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