NCT02640924

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
166

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 7, 2015

Completed
22 days until next milestone

First Posted

Study publicly available on registry

December 29, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2021

Completed
Last Updated

March 21, 2016

Status Verified

March 1, 2016

Enrollment Period

2.9 years

First QC Date

December 7, 2015

Last Update Submit

March 18, 2016

Conditions

Carcinoma, Hepatocellular

Keywords

Hepatocellular carcinomaProton therapyRadiation therapySwitching control radiofrequency ablation

Outcome Measures

Primary Outcomes (1)

  • Local control rate (treatment in-field control rate)

    3-year

Secondary Outcomes (14)

  • Overall survival rate

    3-year

  • Intrahepatic control rate

    3-year

  • Distant metastasis free survival rate

    3-year

  • Local control rate (treatment in-field control rate)

    5-year

  • Overall survival rate

    5-year

  • +9 more secondary outcomes

Study Arms (2)

Proton radiotherapy

EXPERIMENTAL

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

Radiofrequency Ablation

EXPERIMENTAL

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

Interventions

Proton radiotherapyRADIATION
Proton radiotherapy
Radiofrequency AblationPROCEDURE
Radiofrequency Ablation

Eligibility Criteria

Age20 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 333, Taiwan

RECRUITING

Related Publications (5)

  • Kan Z, Zheng H, Liu X, Li S, Barber TD, Gong Z, Gao H, Hao K, Willard MD, Xu J, Hauptschein R, Rejto PA, Fernandez J, Wang G, Zhang Q, Wang B, Chen R, Wang J, Lee NP, Zhou W, Lin Z, Peng Z, Yi K, Chen S, Li L, Fan X, Yang J, Ye R, Ju J, Wang K, Estrella H, Deng S, Wei P, Qiu M, Wulur IH, Liu J, Ehsani ME, Zhang C, Loboda A, Sung WK, Aggarwal A, Poon RT, Fan ST, Wang J, Hardwick J, Reinhard C, Dai H, Li Y, Luk JM, Mao M. Whole-genome sequencing identifies recurrent mutations in hepatocellular carcinoma. Genome Res. 2013 Sep;23(9):1422-33. doi: 10.1101/gr.154492.113. Epub 2013 Jun 20.

    PMID: 23788652BACKGROUND

  • Mizumoto M, Okumura T, Hashimoto T, Fukuda K, Oshiro Y, Fukumitsu N, Abei M, Kawaguchi A, Hayashi Y, Ookawa A, Hashii H, Kanemoto A, Moritake T, Tohno E, Tsuboi K, Sakae T, Sakurai H. Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1039-45. doi: 10.1016/j.ijrobp.2010.07.015. Epub 2010 Oct 1.

    PMID: 20888707RESULT

  • Seror O, N'Kontchou G, Ibraheem M, Ajavon Y, Barrucand C, Ganne N, Coderc E, Trinchet JC, Beaugrand M, Sellier N. Large (>or=5.0-cm) HCCs: multipolar RF ablation with three internally cooled bipolar electrodes--initial experience in 26 patients. Radiology. 2008 Jul;248(1):288-96. doi: 10.1148/radiol.2481071101. Epub 2008 May 15.

    PMID: 18483229RESULT

  • Lee J, Lee JM, Yoon JH, Lee JY, Kim SH, Lee JE, Han JK, Choi BI. Percutaneous radiofrequency ablation with multiple electrodes for medium-sized hepatocellular carcinomas. Korean J Radiol. 2012 Jan-Feb;13(1):34-43. doi: 10.3348/kjr.2012.13.1.34. Epub 2011 Dec 23.

    PMID: 22247634RESULT

  • Lee JM, Han JK, Kim HC, Kim SH, Kim KW, Joo SM, Choi BI. Multiple-electrode radiofrequency ablation of in vivo porcine liver: comparative studies of consecutive monopolar, switching monopolar versus multipolar modes. Invest Radiol. 2007 Oct;42(10):676-83. doi: 10.1097/RLI.0b013e3180661aad.

    PMID: 17984764RESULT

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiofrequency Ablation

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Radiofrequency TherapyTherapeuticsAblation TechniquesSurgical Procedures, Operative

Study Officials

  • Shi-Ming Lin, MD

    Chang Gung Memorial Hospital

    STUDY CHAIR

Central Study Contacts

Bing-Shen Huang, MD

CONTACT

+886-3-3281200beanson.tw@gmail.com

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Liver Research Unit

Study Record Dates

First Submitted

December 7, 2015

First Posted

December 29, 2015

Study Start

January 1, 2016

Primary Completion

December 1, 2018

Study Completion

December 1, 2021

Last Updated

March 21, 2016

Record last verified: 2016-03

Locations

TW(1)