Radiofrequency Ablation in Treating Patients With Liver Cancer and Cirrhosis

Study Overview
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Brief Summary
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RATIONALE: Radiofrequency ablation uses a high-frequency, electric current to kill tumor cells. CT-, MRI-, or ultrasound-guided radiofrequency ablation may be an effective treatment for liver cancer and cirrhosis. PURPOSE: This phase II trial is studying how well radiofrequency ablation works in treating patients with liver cancer and cirrhosis.

Detailed Description
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OBJECTIVES: Primary Determine the 18-month successful disease control rate, defined as no identifiable liver tumor by CT scan, in patients with hepatocellular carcinoma and cirrhosis treated with solitary or repetitive percutaneous radiofrequency ablation (RFA). Secondary Correlate tumor size, MELD score, and the number of RFA treatments (solitary or repetitive) with the 18-month successful disease control rate in patients treated with this procedure. Determine the local and remote intrahepatic and extrahepatic tumor recurrence rates in patients treated with this procedure. Correlate local and remote intrahepatic and extrahepatic tumor recurrence rates with the 18-month successful disease control rate in patients treated with this procedure. Correlate tumor size with the local disease control rate in patients treated with this procedure. Correlate solitary or repetitive RFA with or without local/regional tumor control with the development of extrahepatic tumor in these patients. Determine the local tumor eradication rate, as determined by examination of whole liver specimens or CT scan, in patients treated with this procedure. OUTLINE: This is a multicenter study. Patients are stratified according to hepatic dysfunction using the MELD score (< 15 vs 15-25 vs > 25). Patients undergo placement of an ablation electrode percutaneously into the tumor(s) by CT scan, MRI, or ultrasound guidance. Patients then undergo percutaneous radiofrequency ablation (RFA) directly to the tumor(s) for 12 minutes. Patients undergo CT scan of the liver within 1 week after RFA treatment and then every 3 months for up to 18 months. Patients with residual or recurrent intrahepatic tumor(s) detectable on the 3-month or subsequent CT scan undergo repeat RFA as is technically feasible and clinically indicated for up to 15 months after initial RFA treatment. After completion of study treatment, patients are followed at 1 day, 1 week, 1 month, and then every 3 months for up to 18 months. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Official Title
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Multicenter Feasibility Study of Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in Cirrhotic Patients

Conditions
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Liver Cancer

Intervention / Treatment
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* Device: radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of hepatocellular carcinoma (HCC), meeting 1 of the following criteria: Histologically confirmed HCC Discrete non-biopsied hepatic tumors, meeting 1 of the following criteria: Hypervascular tumor > 2 cm by 2 imaging studies Hypervascular tumor > 2 cm by a single imaging study AND alpha-fetoprotein ≥ 400 ng/mL Discrete non-biopsied hypervascular hepatic tumors by 2 consecutive imaging studies (e.g., CT scan or MRI) with documented tumor growth > 1 cm in diameter Histologically confirmed cirrhosis OR typical findings of cirrhosis (i.e., nodular liver, splenomegaly, varices, or ascites) by CT scan and/or MRI scan Single hepatic tumor > 3.0 cm but ≤ 5.0 cm in diameter OR 3 or fewer hepatic tumors ≤ 3.0 cm in diameter No excessive intrahepatic tumor burden (i.e., > 3 hepatic tumors OR a single hepatic tumor > 5 cm OR more than 3 vague hypervascular nodules > 1 cm) Tumor(s) ≥ 1 cm from the main, right, and left portal veins and hollow viscera No hepatic or portal vein tumor invasion Tumor(s) > 1 cm treatable by percutaneous radiofrequency ablation No extrahepatic tumor Not a surgical candidate due to any of the following reasons: Tumor in an unresectable location Comorbid disease Insufficient hepatic reserve PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic No uncorrectable coagulopathy Hepatic Not specified Renal Creatinine ≤ 2.0 mg/dL Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No active symptomatic bacterial or fungal infection that is newly diagnosed and/or requires treatment No absolute contraindication to IV iodinated contrast (i.e., history of significant contrast reaction not mitigated by appropriate premedication) PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior or concurrent chemotherapy for HCC No prior or concurrent chemoembolization for HCC Endocrine therapy Not specified Radiotherapy No prior or concurrent radiotherapy for HCC Surgery No prior choledochoenteric anastomosis No prior sphincterotomy of duodenal papilla Other No prior or concurrent cryoablation for HCC No other prior or concurrent therapy for HCC At least 7 days since prior aspirin At least 24 hours since prior ibuprofen At least 12 hours since prior low molecular weight heparin preparations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All Patients<br>patients with cirrhosis undergoing solitary or repetitive percutaneous RFA treatment sessions for the treatment of HCC. | Device: radiofrequency ablation<br> <br> * Other names: RFA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Successful Control of Disease at 18 Months | Outcome is positive (success) if alive and no disease is observed by CT at 18 months post start of therapy Outcome is negative if the patient was deceased or disease was observed by CT at 18 months post start of therapy Success rate it the fraction of eligible patients who were alive and disease free at 18 months. | 18 months after start of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Success in Those Who Received Solitary vs Repetitive Radiofrequency Ablation | this outcome measures the impact of Solitary vs repetitive radiofrequency ablation on success. Success is defined as the number of patients centrally determined to be alive and tumor-free 18 months after start of therapy, corrected for repetitive RFA. | 18 months after start of therapy | 
| Effect of Tumor Size on Successful Control of Disease at 18 Months | Outcome is positive (success) if alive and no disease is observed by CT at 18 months post start of therapy Outcome is negative if the patient was deceased or disease was observed by CT at 18 months post start of therapy Success rate it the fraction of eligible patients who were alive and disease free at 18 months. Tumor size is a continuous variable as measured at imaging. | 18 months after start of therapy | 
| Local Tumor Recurrence (Control) Rates | local tumor control rate is defined as a tumor that was ablated and was not seen again within the 18 month period | 18 months after start of therapy | 
| Impact of Tumor Size on Local Control Rates | Lesion level local control is defined as a success if a tumor is ablated and does not recur in 18 mo. | 18 months after start of therapy | 
| Development of Extra-hepatic Tumor | Whether or not extrahepatic tumors were seen at 18months post ablation will be compared with the number of RFA sessions. | 18 months after start of therapy | 
| Local Tumor Eradication Rate by Examination of Liver Via Autopsy or Transplant vs That Determined by CT Scan | the primary outcome was evidence of existing tumor on pathologic review of the liver at the time or transplant or autopsy within the 18 month observational period. This outcome was compared to the CT HCC detection. | 18 months after start of therapy | 
| Remote Tumor Occurrence Rates | remote tumor occurrence rate is defined as a new intrahepatic tumor that developed remote from the ablation site within the 18 month period | 18 months after start of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer