Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry NCI-04-C-0263 CELSION-10403101, NCT00093444

Objectives

1. 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.
2. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Platelet count ≥ 75,000/mm³
• WBC ≥ 1,500/mm³
• 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

Expected Enrollment

Approximately 30 patients will be accrued for this study within 2 years.

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

Effects of ablative therapy on tumor blood flow and tumor vascular density as measured by MRI at 28 days following study completion

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Bradford Wood, MD, Protocol chair		Ph: 301-496-7739 Email: bwood@nih.gov

Related Information

Web site for additional information

Registry Information
Official 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
Trial Start Date		2004-09-07
Registered in ClinicalTrials.gov		NCT00093444
Date Submitted to PDQ		2004-08-16
Information Last Verified		2007-04-29