A Phase I Dose Escalation Study Of Heat Activated Liposome Delivery Of Doxorubicin And Radiofrequency Ablation Of Primary And Metastatic Tumors Of The Liver
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Maximum tolerated dose of heat-activated doxorubicin HCL liposome
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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:
- •18 and over
- •Performance status
- •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)
- •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])
- •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
- •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
- •See Disease Characteristics
- •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
- +15 more not shown
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
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 Outcomes
- Effects of ablative therapy on tumor blood flow and tumor vascular density as measured by MRI at 28 days following study completion