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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma(HCC)

Intervention / Treatment
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* Radiation: Stereotactic ablative radiotherapy (SABR)
* Procedure: Re-Transcatheter arterial chemoembolization (re-TACE)


Participation Criteria
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Eligibility Criteria
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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 ： Hemoglobin ≧ 8.0 g/dL(may be post-transfusion if clinically indicated) Total bilirubin ≦ 3.0 mg/dL Aspartate aminotransferase (AST) ≦ 5x institutional upper limit of normal Alanine transaminase (ALT) ≦ 5x institutional upper limit of normal Absolute neutrophil count ≧ 1,000 /μl Platelet count ≧ 20,000/μl (may be post-transfusion if clinically indicated) 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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Stereotactic ablative radiotherapy (SABR) | Radiation: Stereotactic ablative radiotherapy (SABR)<br>* 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.<br>* Other names: Stereotactic Body Radiation Therapy (SBRT);|
| Active Comparator: Arm II<br>Re-transcatheter arterial chemoembolization (re-TACE) | Procedure: Re-Transcatheter arterial chemoembolization (re-TACE)<br>* Patients with HCC after incomplete TACE are randomized to further re-TACE.<br>* Other names: Transarterial Chemoembolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Grade of toxicity | To estimate the rate of acute and late treatment-related toxicity related to specific symptoms | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Transcatheter Arterial Chemoembolization (TACE), Stereotactic ablative radiotherapy (SABR)