Proton Radiotherapy Versus Radiofrequency Ablation for Patients With Medium or Large Hepatocellular Carcinoma

March 18, 2016 updated by: Shi-Ming Lin, Chang Gung Memorial Hospital

Proton Beam Radiotherapy Versus Switching Control Radiofrequency Ablation for Patients With Medium (>3, ≦5 cm) or Large (>5, ≦7cm) Treatment-naive Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan, where chronic viral hepatitis is common. Patients with HCC typically have impaired liver function because of virus- or alcohol- induced cirrhosis and viral hepatitis, and only approximately 20% of them are appropriate candidates for surgery. The 5-year overall survival for patients treated by surgery is approximately 30%-70%. For those not treated with surgery, liver function affected by an underlying liver disease has a strong influence on clinical outcomes, and complicates treatment strategies further than for other tumors. Maximal preservation of normal liver volume and function is an important consideration in the choice of treatment.

Proton beam has been applied to HCC treatment in Japan for longer than a decade, and several retrospective results showed excellent 3-5 years local control rate ranging from 85-95% and nearly no major complications. The investigators also retrospectively reviewed 75 index tumors sized 3.1-7.0cm in 70 patients receiving multiple-electrode radiofrequency ablation with switching controller (ME-SWC RFA) treatments in the period between 1 January 2009 and 31 December 2011 (Oral report in Taiwan Digestive Disease Week, October, 2012). Estimated 1-, 2-, and 3-year cumulative overall survival rates and local control rates were 94%, 85%, 81% and 89%, 83%, 67%, respectively.

Since ME-SWC RFA is the present one of standard modalities for non-surgery, moderate to larger (3-7 cm) HCC, and based on retrospective studies the local control rate of proton therapy was better than radiofrequency ablation, this prospective trial is aimed to compare the effects of these two modalities in 3-7 cm HCC patients who are not candidates for surgery or refuse surgery. This prospective study has high possibility to confirm the role of proton beam in HCC.

Along with the clinical trial, the investigators will also use next generation sequencing (NGS) to exam gene expression profile of tumor samples and find out candidate genes related to local control, intrahepatic control (treatment out-field control in liver), regional lymph node relapse, distant metastasis, and treatment response in HCC.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

166

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taoyuan, Taiwan, 333
        • Recruiting
        • Chang Gung Memorial Hospital, Linkou
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically confirmed hepatocellular carcinoma or lesion with typical triphasic CT or MRI imaging features for HCC
  • Single tumor and tumor size > 3cm, ≦7cm in diameter
  • Patients are unsuitable for resection or unwilling to accept surgery.
  • Age ≥20 years old
  • Eastern Cooperative Oncology Group performance status score of 0 or 1
  • Child-Pugh score ≦ 8
  • Willing to sign informed consent regarding participation in this study

Exclusion Criteria:

  • Patients have received any treatment for HCC before this study
  • Pregnancy/breast feeding women
  • Tumor adjacent to bowel <1cm
  • Extrahepatic metastasis
  • Extrahepatic invasion
  • Portal or hepatic vein tumor invasion/thrombosis
  • Uncontrolled ascites
  • Glomerular filtration rate (GFR) < 30 ml/min*
  • Platelet count < 50,000/L*
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 5 years
  • Ongoing medically significant active infection.
  • MRI incompatible devices
  • * Baseline laboratories results must be within the protocol range prior to sign informed consent. Repeat lab tests are permitted to evaluate eligibility during the Screening Period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Proton radiotherapy
Proton radiotherapy will be totally 66 cobalt gray equivalent (CGE) in 10 fractions and delivered once daily, 5 fractions per week, over 2 weeks for HCC more than 1 cm away from the alimentary tract.
Radiation: Proton radiotherapy
Experimental: Radiofrequency Ablation
Multiple-electrode radiofrequency with switch-controller system (ME-SWC RFA) can create a large coagulation necrosis volume and successful treat HCC sized more than 3 cm, extending to 8.5 cm. ME-SWC RFA system uses up to 3 electrodes parallel insertion to inside of the tumors with an equilateral triangular confirmation before initiation of ablation. The distances between electrodes are about 1.5-2 cm, estimated by ultrasound measuring. The switching machine is set on the auto-mode, and all electrodes work alternately and switching each other automatically after impendence surge.
Procedure: Radiofrequency Ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Local control rate (treatment in-field control rate)
Time Frame: 3-year
3-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival rate
Time Frame: 5-year
5-year
Overall survival rate
Time Frame: 3-year
3-year
Intrahepatic control rate
Time Frame: 3-year
3-year
Distant metastasis free survival rate
Time Frame: 3-year
3-year
Local control rate (treatment in-field control rate)
Time Frame: 5-year
5-year
Intrahepatic control rate
Time Frame: 5-year
5-year
Distant metastasis free survival rate
Time Frame: 5-year
5-year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 3-year
3-year
Patient report outcome - quality of life as assessed by the functional assessment of cancer therapy - hepatobiliary (FACT-Hep)
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year
Patient report outcome - fatigue as assessed by the functional assessment of cancer therapy (FACT-F)
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year
Patient report outcome - pain as assessed by the brief pain inventory-short form (BPI-SF)
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year
Patient report outcome - symptom distress as assessed by the Memorial symptom assessment scale-short form (MSAS-SF)
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year
Patient report outcome - treatment satisfaction as assessed by the functional assessment of chronic illness therapy-treatment satisfaction-general (FACIT-TS-G)
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year
Patient report outcome - quality of life as assessed by the EQ-5D-3L
Time Frame: 3-year
The data will be collected 17 times from enrollment to the 36th month after treatment. Specific measurement points are: baseline, day 3, day 7, day 14, month 1, month 3, then every 3 months to the 36th month after treatment.
3-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chang Gung Memorial Hospital

Investigators

  • Study Chair: Shi-Ming Lin, MD, Chang Gung Memorial Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

December 7, 2015

First Submitted That Met QC Criteria

December 23, 2015

First Posted (Estimate)

December 29, 2015

Study Record Updates

Last Update Posted (Estimate)

March 21, 2016

Last Update Submitted That Met QC Criteria

March 18, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 103-1278A3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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