Radiofrequency Ablation in Treating Patients With Unresectable Primary or Metastatic Liver Cancer

The Use of Radiofrequency Ablation to Treat Hepatic Neoplasms

RATIONALE: Radiofrequency ablation is a procedure that heats tumors to several degrees above body temperature and may kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of radiofrequency ablation in treating patients who have unresectable primary or metastatic liver cancer.

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Metastatic Cancer; Liver Cancer
• Intervention / Treatment: Procedure: computed tomography; Procedure: magnetic resonance imaging; Procedure: positron emission tomography; Procedure: radiofrequency ablation; Procedure: radionuclide imaging; Procedure: ultrasound imaging; Radiation: fludeoxyglucose F 18 (FDG-PET); Radiation: gadopentetate dimeglumine

Detailed Description

OBJECTIVES:

• Evaluate the nature and duration of response of patients with primary or metastatic liver neoplasms, who are not candidates for surgical resection, treated with radiofrequency interstitial tissue ablation.
• Evaluate the ability of dynamic magnetic resonance imaging (MRI) to assess the effects of this therapy on tumor blood flow and tumor vascular density in these patients.
• Determine the ability of positron emission tomography with fludeoxyglucose F 18 (FDG-PET) to monitor response after treatment with this therapy in these patients.
• Compare FDG-PET results with computed tomography (CT) scan, biopsy, and serum marker results in patients treated with this therapy.
• Compare the performance of FDG-PET with CT scan and MRI, in terms of their ability to assess the efficacy of this therapy in these patients.

OUTLINE: Lesions are targeted by ultrasound and then radiofrequency ablation needles are inserted into the lesions and heated to a target temperature greater than 60 degrees C for 15 minutes, though exposure time may vary depending on temperatures achieved. To achieve a 1 cm margin of ablated tissue around each lesion, multiple ablation courses may be performed, depending on the size of the lesions and the time required to complete the treatment.

Patients undergo magnetic resonance imaging with gadopentetate dimeglumine contrast, CT scan, ultrasound, and positron emission tomography with fludeoxyglucose F 18 at baseline, 6 weeks, every 3 months for 1 year, and then every 6 months for 2 years.

Patients are followed at 6 weeks, every 3 months for 1 year, and then every 6 months for 2 years or until evidence of recurrence.

PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study within 6 years.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary or metastatic liver lesions

  • Not a candidate for surgical resection
• Must have six or fewer lesions and no single lesion greater than 7 cm in diameter
• Extrahepatic disease allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Platelet count at least 50,000/mm^3
• Prothrombin time (PT) or partial thromboplastin time (PTT) no greater than 1.5 times control (except for therapeutically anticoagulated nonrelated medical conditions [e.g., atrial fibrillation])

Hepatic:

• Bilirubin no greater than 3.0 mg/dL

Renal:

• Creatinine no greater than 2.5 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• No pacemakers, cerebral aneurysm clips, shrapnel injury, or implantable electronic devices
• No known uncontrollable serious reactions (e.g., anaphylaxis) to contrast agents used in this study
• Weight less than 136 kg

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Concurrent systemic therapy for extrahepatic disease is allowed only if begun prior to radiofrequency ablation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiofrequency ablation in liver cancer; This trial is designed to gain experience with the use of ablation devices with liver tumors. Radiofrequency ablation is a procedure that heats tumors to several degrees above body temperature and may kill tumor cells.

Procedure: computed tomography; Scan to assess the effects of ablation.; Procedure: magnetic resonance imaging; Imaging used to assess the effects of this ablative therapy on tumor vascular density.; Procedure: positron emission tomography; Physiology based method of imaging disease based on uptake and metabolism of radiopharmaceutical by the tissues.; Procedure: radiofrequency ablation; Radiofrequency ablation uses saline infusion into and out of needle/electrode through a closed system. More energy may be deposited without tissue-charring or gas vaporization.; Procedure: radionuclide imaging; Imaging following injection of a radioactive material.; Procedure: ultrasound imaging; An ultrasound (e.g. sound waves) is used to identify the lesion and needle placement.; Radiation: fludeoxyglucose F 18 (FDG-PET); FDG PET scans rely on metabolic changes to evaluate response to therapy.; Radiation: gadopentetate dimeglumine; Food and Drug Administration approved contrast agent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Response

Standard response criteria will be used to assess the CT (computed tomography) scan images on a lesion per lesion basis. Complete response is complete disappearance of the index lesion on followup scan when compared to the pretreatment images. Partial response is a decrease of 50% or greater in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images. Minor response is a decrease between 25% and 49% in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images. Stable disease is no change in the size of the treated lesion. Progressive disease is an increase of greater than 25% in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.	9 years, 9 months
Tumor Blood Flow	Tumor blood flow was to be assessed by magnetic resonance imaging (MRI) and compared to data collected on baseline pretreatment images and other appropriate time points for changes in tumor microvascular density.	Baseline, 3 months, and 6 months following treatment
Tumor Vascular Density	Tumor vascular density was to be assessed by magnetic resonance imaging (MRI) and compared to data collected on baseline pretreatment images and other appropriate time points for changes in tumor microvascular density. Patterns of MRI contrast uptake within tumors correlate with microvessel density.	Baseline, 3 months, and 6 months following treatment
Percentage of Participants With a Response Using Fludeoxyglucose (18F) - Positron Emission Tomography (FDG-PET) Following Radiofrequency Ablation (RFA)	Response was to be evaluated by the standard response criteria. Complete response is the complete disappearance of the index lesion on follow-up scan when compared to the pretreatment images. Partial response is a decrease of 50% or greater in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images. Minor response is a decrease between 25% and 49% in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images. Stable disease is no change in the size of the treated lesion. Progressive disease is an increase of greater than 25% in the product of the perpendicular diameters of the measured lesion following treatment compared to the pretreatment images.	Baseline, 6 weeks, 3 months, and 6 months following treatment
Compare Fludeoxyglucose (18F) Positron-Emission Tomography (FDG-PET) Results With Computed Tomography (CT)	Participants were to undergo FDG-PET scanning and CT scans to compare changes in size of metabolically active volume and standard uptake value (tumor metabolism).	Baseline, 6 weeks, 3 months, and 6 months following treatment
Compare Fludeoxyglucose (18F) Positron-Emission Tomography (FDG-PET) Results With Biopsies	Participants were to undergo tissue biopsies of tumor to quantify changes in the tumor to see if the changes we see on the imaging studies are the same as the changes in the tumor.	Baseline, 6 weeks, 3 months, and 6 months following treatment
Compare Fludeoxyglucose (18F) Positron-Emission Tomography (FDG-PET) Results With Serum Markers	Images obtained by the FDG-PET was to be processed for changes in measured parameters and quantified compared to serum markers at baseline and appropriate follow-up points.	Baseline, 6 weeks, 3 months, and 6 months following treatment
Compare the Performance of Fludeoxyglucose (18F) Positron-Emission Tomography to Computed Tomography and Magnetic Resonance Imaging With Respect to Their Ability to Assess the Effects of Radiofrequency Ablation on the Treatment of Hepatic Neoplasms	Images obtained by the FDG-PET, MRI and CT was to be processed for changes in measured parameters and quantified compared to baseline (e.g., <median change, >median change in size on CT, computed by subtracting the baseline value from the value at the appropriate follow-up point).	Baseline, 6 weeks, 3 months, and 6 months following treatment
Evaluate the Ability of Fludeoxyglucose (18F) Positron-Emission Tomography (FDG-PET) to Monitor Response Following Radiofrequency Ablation (RFA)	PET scan images was to be read by a physician experienced in the interpretation of whole body PET imaging. The region of interest was to be performed in any abnormal sites of uptake that is a candidate and or has been RFA ablated.	Baseline, 6 weeks, 3 months, and 6 months following treatment

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Steven A Libutti, MD, National Cancer Institute, National Institutes of Health

Study record dates

Study Major Dates

• Study Start: August 1, 1998
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 3, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific; liver metastases; recurrent adult primary liver cancer; localized unresectable adult primary liver cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 990025; 99-C-0025; CDR0000066875

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No