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

Carcinoma, Hepatocellular Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02640924
• Other study ID #: 103-1278A3
• Status: Not yet recruiting
• Phase: Phase 3
• First received: December 7, 2015
• Last updated: December 23, 2015
• Start date: January 2016
• Est. completion date: December 2021

Study information

• Verified date: December 2015
• Source: Chang Gung Memorial Hospital
• Contact: Bing-Shen Huang, MD
• Phone: +886-3-3281200
• Email: beanson.tw[@]gmail.com
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 166
• Est. completion date: December 2021
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed hepatocellular carcinoma OR typical triphasic CT imaging features for HCC

• Single tumor and tumor size > 3cm, ? 7cm in diameter

• Unresectable HCC or patients with resectable HCC but not appropriate for resection (e.g. Indocyanine green (ICG) retention test >15)

• Eastern Cooperative Oncology Group performance status score of 1 or less

• Child-Pugh score ? 7

• The lesion should be detected on ultrasonography

• Patient has signed consent form regarding participation in the study

Exclusion Criteria:

• Patients had previously received any treatment for HCC

• Pregnancy/breast feeding women or plan to pregnant in the subsequent study period (1 to 2 years)

• Tumor adjacent to bowel <1 cm

• Tumor adjacent to diaphragm, bile duct, great vessel <0.5 cm

• Platelet count < 50,000 /L

• Distant metastasis

• Extra-hepatic invasion

• Tumor rupture

• Uncontrolled ascites

• Glomerular filtration rate (GFR) < 30 ml/ min

• Claustrophobia

• Can not tolerate supine position for one hour

• Synchronous malignancy

• Non-MRI comparable devices

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Radiation:
• Proton radiotherapy

Procedure:
• Radiofrequency Ablation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

References & 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. — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local control rate (treatment in-field control rate)		3-year	No
Secondary	Overall survival rate		3-year	No
Secondary	Intrahepatic control rate		3-year	No
Secondary	Distant metastasis free survival rate		3-year	No
Secondary	Local control rate (treatment in-field control rate)		5-year	No
Secondary	Overall survival rate		5-year	No
Secondary	Intrahepatic control rate		5-year	No
Secondary	Distant metastasis free survival rate		5-year	No
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		3-year	Yes
Secondary	Patient report outcome - quality of life as assessed by (1). the functional assessment of cancer therapy - hepatobiliary (FACT-Hep) and (2). the EQ-5D-3L	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	No
Secondary	Patient report outcome - fatigue as assessed by the functional assessment of cancer therapy (FACT-F)	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	No
Secondary	Patient report outcome - pain as assessed by the brief pain inventory-short form (BPI-SF)	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	No
Secondary	Patient report outcome - symptom distress as assessed by the Memorial symptom assessment scale-short form (MSAS-SF)	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	No
Secondary	Patient report outcome - treatment satisfaction as assessed by the functional assessment of chronic illness therapy-treatment satisfaction-general (FACIT-TS-G)	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	No