Radiofrequency Ablation in Treating Patients With Liver Cancer and Cirrhosis (ACRIN-6673)

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Device: radiofrequency ablation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01655
      • UMASS Memorial Cancer Center - University Campus
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • Abramson Cancer Center of the University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • Temple, Texas, United States, 76508
      • Scott and White Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Other: All Patients; patients with cirrhosis undergoing solitary or repetitive percutaneous RFA treatment sessions for the treatment of HCC.	Device: radiofrequency ablation; Other Names: RFA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: American College of Radiology Imaging Network
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Gerald D. Dodd, MD, The University of Texas Health Science Center at San Antonio

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: August 16, 2005
• First Submitted That Met QC Criteria: August 16, 2005
• First Posted (Estimate): August 19, 2005

Study Record Updates

• Last Update Posted (Actual): September 10, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: localized unresectable adult primary liver cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms
• Other Study ID Numbers: CDR0000439446; U01CA080098 (U.S. NIH Grant/Contract); U01CA079778 (U.S. NIH Grant/Contract); ACRIN-6673 (Other Identifier: CIP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes