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

NCT ID: NCT02640924

Last Updated: 2016-03-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2021-12-31

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.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Proton radiotherapy

Intervention Type: RADIATION

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.

Group Type: EXPERIMENTAL

Radiofrequency Ablation

Intervention Type: PROCEDURE

Interventions

Proton radiotherapy

Intervention Type: RADIATION

Radiofrequency Ablation

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Shi-Ming Lin

Director of Liver Research Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shi-Ming Lin, MD

Role: STUDY_CHAIR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital, Linkou

Taoyuan District, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Bing-Shen Huang, MD

Role: CONTACT

beanson.tw@gmail.com

+886-3-3281200 ext. 7000

Facility Contacts

Bing-Shen Huang, MD

Role: primary

beanson.tw@gmail.com

+886-3-328-1200 ext. 7000

Cheng-En Hsieh, MD

Role: backup

rodney445@gmail.com

+886-3-328-1200 ext. 7000

References

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.

Reference Type: BACKGROUND

PMID: 23788652 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20888707 (View on PubMed)

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.

Reference Type: RESULT

PMID: 18483229 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22247634 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17984764 (View on PubMed)

Other Identifiers

103-1278A3

Identifier Type: -

Identifier Source: org_study_id