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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00093444
First received: October 6, 2004
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Metastatic Cancer
Drug: lyso-thermosensitive liposomal doxorubicin
Procedure: radiofrequency ablation
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Maximum tolerated dose of heat-activated doxorubicin HCL liposome [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects of ablative therapy on tumor blood flow and tumor vascular density as measured by MRI at 28 days following study completion [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2004
Study Completion Date: January 2010
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093444

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
China
Queen Mary Hospital - Hong Kong
Hong Kong, China
Sponsors and Collaborators
Investigators
Study Chair: Bradford Wood, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00093444     History of Changes
Obsolete Identifiers: NCT00090805
Other Study ID Numbers: 040263, 04-C-0263, CELSION-10403101, CDR0000387979
Study First Received: October 6, 2004
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
advanced adult primary liver cancer
liver metastases
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Neoplasm Metastasis
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014