Heat Activated Liposomal Doxorubicin and Radiofrequency Ablation in Treating Patients With Primary or Metastatic Liver Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiofrequency ablation uses high-frequency electric current to kill tumor cells. Combining radiofrequency ablation with liposomal doxorubicin may increase the effectiveness of the drug and kill more tumor cells. PURPOSE: This phase I trial is studying the best dose of liposomal doxorubicin when given with radiofrequency ablation in treating patients with primary or metastatic liver tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of heat activated doxorubicin HCl liposome when combined with radiofrequency ablation in patients with primary or metastatic tumors of the liver. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. OUTLINE: This is a dose-escalation study of heat activated doxorubicin HCl liposome. Patients receive doxorubicin HCl liposome IV over 30 minutes. Approximately 15 minutes after the beginning of the doxorubicin HCl liposome infusion, patients undergo radiofrequency ablation with needles inserted into the tumor(s) and heated to the target temperature for approximately 12-60 minutes. Cohorts of 3-6 patients receive escalating doses of heat activated doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. Patients are followed at 28 days, every 3 months for 1 year, and then every 6 months for 2 years. PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study within 2 years.

Official Title
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A Phase I Dose Escalation Study Of Heat Activated Liposome Delivery Of Doxorubicin And Radiofrequency Ablation Of Primary And Metastatic Tumors Of The Liver

Conditions
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Liver Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: lyso-thermosensitive liposomal doxorubicin
* Procedure: radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed tumor of the liver Primary or metastatic disease No more than 4 lesions No single lesion > 7 cm in maximum diameter Not a candidate for curative surgical resection due to tumor histology or prior surgery PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 3 months Hematopoietic Platelet count ≥ 75,000/mm^3 WBC ≥ 1,500/mm^3 Hemoglobin ≥ 10 g/dL (transfusions to attain levels ≥ 10g/dL allowed) Hepatic Bilirubin ≤ 2.0 mg/dL PT or PTT ≤ 1.5 times control (except for patients receiving anticoagulation therapy for an unrelated medical condition [e.g., atrial fibrillation]) Renal Creatinine ≤ 2.5 mg/dL Cardiovascular See Hepatic Ejection fraction ≥ 50% by MUGA No congestive heart failure No myocardial infarction within the past 6 months No cerebral vascular accident within the past 6 months No life-threatening cardiac arrhythmia Other Weight < 136 kg Glucose ≤ 300 mg/dL No uncontrolled diabetes No known serious uncontrolled reaction (e.g., anaphylaxis) to contrast agents used in this study No known allergy to egg or egg products No other serious medical illness Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent interferon No live vaccines (for immunosuppressed patients only) during and for 30 days after study treatment Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery See Disease Characteristics Other More than 3 weeks since prior therapy for liver tumor(s) More than 3 weeks since prior systemic therapy for non-life-threatening extrahepatic disease and recovered No other concurrent systemic therapy No administration of any of the following medications during and for 30 days after study treatment: Cyclosporine Phenobarbital Phenytoin Streptozocin No concurrent administration of any of the following medications: Amphotericin B by injection Antithyroid agents for overactive thyroid Azathioprine Chloramphenicol Colchicine Flucytosine Ganciclovir Plicamycin Zidovudine Probenecid Sulfinpyrazone

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: lyso-thermosensitive liposomal doxorubicin|nan|
|Procedure: radiofrequency ablation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of heat-activated doxorubicin HCL liposome |  |  | 
| Pharmacokinetics and pharmacodynamics of heat-activated doxorubicin HCL liposome at 15, 30, 45, 60, 75, and 90 minutes; 2, 3, 4, 6, 24, and 46 hours; and 4 and 8 days following infusion |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of ablative therapy on tumor blood flow and tumor vascular density as measured by MRI at 28 days following study completion |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced adult primary liver cancer, liver metastases, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer