Comparing Re-TACE Versus SABR for Post-prior-TACE Incompletely Regressed HCC: a Randomized Controlled Trial (TASABR)

Hepatocellular Carcinoma(HCC) Clinical Trial

— TASABR  

Official title:

Comparing Re-trans-catheter Arterial Chemoembolization Versus Stereotactic Ablative Radiotherapy for Hepatocellular Carcinoma Patients Who Had Incomplete Response After Prior TACE (TASABR Trial): a Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02921139
• Other study ID #: A10502001
• Status: Recruiting
• Phase: N/A
• Start date: November 2016
• Est. completion date: November 2022

Study information

• Verified date: August 2021
• Source: Dalin Tzu Chi General Hospital
• Contact: Shih-Kai Hung, PhD
• Phone: +886-5-2648000
• Email: oncology158[@]yahoo.com.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Till now, trans-arterial chemoembolization (TACE) is still one of the common modalities in treating hepatocellular carcinoma patients with unresectable intermediate stage. However, residual viable HCC after TACE is not uncommon, leading to a poor overall survival after TACE alone. Recently, stereotactic ablative radiotherapy (SABR) has been reported to be potentially useful for curatively managing early-stage HCC in retrospective studies. Thus, conducting a randomized clinical trial to test the role of SABR in eradicating post-TACE residual tumors is therefore encouraged. The present phase-III trial intended to compare clinical outcomes between TACE + SABR and TACE + re-TACE for HCC patients with post-prior-TACE residual tumors.

Description:

Developing effective treatment modalities is crucial in managing HCC patients with unresectable intermediate stage. Nowadays, many therapies have been used for treating this group of HCC patients, including TACE. However, residual tumors after TACE are not uncommon. In conventional, re-TACE is recommended for managing residual tumors. However, accumulated overall survival is still poor in consecutive TACEs, leading to a low rate of <20% in 5 years. In this regard, radiotherapy has been proved to be effective in managing HCC patients, especially a novel technique named SABR. When compared with conventional-fractionated radiotherapy, SABR demonstrated better treatment responses with fewer side effects in managing primary or metastatic liver tumors. In the literature, phase I and II trials of TACE plus SABR showed excellent local control rates and promising 1- and 2-year survival rates. However, till now, there is no head-to-head comparison between TACE + SABR and consecutive TACEs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Patient has a) Radiographic enhancing liver lesions with early enhance and delay wash out on triple phase CT or MRI or b) histological confirmation of HCC as determined by the Liver Tumor Board
• Age ? 20
• Genders: Both male and female
• Barcelona Clinic Liver Cancer (BCLC) stage A to B
• Child-Pugh A or B
• Unresectable tumors or medically inoperable status or surgery was declined/refused.
• Meets clinical criteria for eligibility for TACE or SABR
• SABR can be applied within 6 weeks of registration
• Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Life expectancy > 12 weeks
• negative pregnancy
• No prior treatment, except for surgical resection and radiofrequency ablation (RFA)
• Lab :

1. Hemoglobin ? 8.0 g/dL(may be post-transfusion if clinically indicated)

2. Total bilirubin ? 3.0 mg/dL

3. Aspartate aminotransferase (AST) ? 5x institutional upper limit of normal

4. Alanine transaminase (ALT) ? 5x institutional upper limit of normal

5. Absolute neutrophil count ? 1,000 /µl

6. Platelet count ? 20,000/µl (may be post-transfusion if clinically indicated)

7. Prothrombin time-international normalized ratio = 1.7

Exclusion Criteria:

• Previous TACE = 2 times
• Prior radiotherapy to the upper abdomen
• Prior invasive malignancy other than primary liver malignancy (except non-melanomatous skin cancer) unless disease free for at least 3 years
• metastatic disease
• cardiac ischemia or stroke within last 6 months
• medical or psychosocial condition unsuitable
• History of sorafenib therapy within 21 days prior

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma(HCC)

Intervention

Radiation:
• Stereotactic ablative radiotherapy (SABR)
Patients with HCC after incomplete TACE are randomized to stereotactic ablative radiotherapy (SABR). SABR will be delivered in 5 fractions.The preferred inter-fraction time interval is 48 hours. The entire treatment with 10 days is preferred.

Procedure:
• Re-Transcatheter arterial chemoembolization (re-TACE)
Patients with HCC after incomplete TACE are randomized to further re-TACE.

Locations

Country	Name	City	State
Taiwan	Dalin Tzu Chi Hospital	Chiayi City

Sponsors (3)

Lead Sponsor	Collaborator
Dalin Tzu Chi General Hospital	Buddhist Tzu Chi General Hospital, Hualien Tzu Chi General Hospital

Country where clinical trial is conducted

Taiwan, 

References & Publications (6)

Chang IC, Huang SF, Chen PJ, Chen CL, Chen CL, Wu CC, Tsai CC, Lee PH, Chen MF, Lee CM, Yu HC, Lo GH, Yeh CT, Hong CC, Eng HL, Wang J, Tseng HH, Hsiao CH, Wu HI, Yen TC, Liaw YF. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network. Medicine (Baltimore). 2016 Apr;95(15):e3284. doi: 10.1097/MD.0000000000003284. — View Citation

Cheng X, Sun P, Hu QG, Song ZF, Xiong J, Zheng QC. Transarterial (chemo)embolization for curative resection of hepatocellular carcinoma: a systematic review and meta-analyses. J Cancer Res Clin Oncol. 2014 Jul;140(7):1159-70. doi: 10.1007/s00432-014-1677-4. Epub 2014 Apr 22. Review. — View Citation

Huo YR, Eslick GD. Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. JAMA Oncol. 2015 Sep;1(6):756-65. doi: 10.1001/jamaoncol.2015.2189. Review. — View Citation

Kang JK, Kim MS, Cho CK, Yang KM, Yoo HJ, Kim JH, Bae SH, Jung DH, Kim KB, Lee DH, Han CJ, Kim J, Park SC, Kim YH. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012 Nov 1;118(21):5424-31. doi: 10.1002/cncr.27533. Epub 2012 May 8. — View Citation

Takeda A, Sanuki N, Tsurugai Y, Iwabuchi S, Matsunaga K, Ebinuma H, Imajo K, Aoki Y, Saito H, Kunieda E. Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation. Cancer. 2016 Jul 1;122(13):2041-9. doi: 10.1002/cncr.30008. Epub 2016 Apr 8. — View Citation

Wahl DR, Stenmark MH, Tao Y, Pollom EL, Caoili EM, Lawrence TS, Schipper MJ, Feng M. Outcomes After Stereotactic Body Radiotherapy or Radiofrequency Ablation for Hepatocellular Carcinoma. J Clin Oncol. 2016 Feb 10;34(5):452-9. doi: 10.1200/JCO.2015.61.4925. Epub 2015 Nov 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	freedom form local progression	The freedom from local progression is defined as no in-field progressive disease. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks	Up to 12 months
Secondary	Overall survival	To estimate the rates of overall survival. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks	Up to 24 months
Secondary	Progression-free survival	To estimate the rates of progression-free survival. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks	Up to 24 months
Secondary	Response rate	To estimate the response rate. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks	Up to 24 months
Secondary	Duration of Response of the treated tumor	The duration of the response is from the time response is achieved until disease progression is detected. It will be estimated by Kaplan-Meier and Cox regression model adjusting for the competing risks	Up to 24 months
Secondary	Grade of toxicity	To estimate the rate of acute and late treatment-related toxicity related to specific symptoms	Up to 24 months