DEB-TACE Plus Lenvatinib or Sorafenib or PD-1 Inhibitor for Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Transarterial chemoembolization (TACE) based on drug-eluting beads (DEB-TACE) is widely used for unresectable hepatocellular carcinoma (HCC). However, the long-term survival is still low after DEB-TACE treatment. In recent years, lenvatinib and anti-PD-1 have exhibited potential therapeutic effects for advanced HCC. And sorafenib is the standard drug for advanced HCC. Combining targeted drugs or immunotherapies with DEB-TACE may provide synergistic effects and facilitate the development of personalized medicine. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Detailed Description
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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Most patients with HCC are diagnosed as advanced stage or unresectable disease because of the lack of signs and symptoms. Despite significant research efforts, only a few effective treatment approaches have been developed for HCC. Conventional transarterial chemoembolization (cTACE) is widely used as a palliative treatment for inoperable HCC. TACE based on drug-eluting beads (DEB-TACE) has recently been introduced into the clinic. This technique relies on drug-loaded microspheres to embolize and release antitumor medication gradually and locally in order to maximize local ischemia and tumor necrosis. Nowadays, many RCTs and meta-analyses found DEB-TACE is associated with higher overall survival than cTACE for unresectable HCC. However, the long-term survival is still low after DEB-TACE treatment. In recent years, targeted drugs (such as sorafenib, lenvatinib) and immune checkpoint inhibitor (anti-PD-1) have exhibited potential therapeutic effects for advanced HCC. Lenvatinib is non-inferior to sorafenib in overall survival in untreated advanced HCC. Combining targeted drugs or immunotherapies with conventional therapeutic approaches may provide synergistic effects and facilitate the development of personalized medicine. However, it is still unknown which is the best combining treatment. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Official Title
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Drug-eluting Bead Transarterial Chemoembolization Plus Lenvatinib or Sorafenib or PD-1 Inhibitor for Unresectable Hepatocellular Carcinoma: a Multicentric Prospective Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: DEB-TACE plus Sorafenib
* Drug: DEB-TACE plus Lenvatinib
* Drug: DEB-TACE plus PD-1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 75 years Patients with unresectable primary hepatocellular carcinoma. With Child-Pugh A liver function. Exclusion Criteria: Patients received targeted drugs, anti-PD1, or anti-PD-L1 treatment. Patients with recurrent hepatocellular carcinoma. Patient compliance is poor. The blood supply of tumor lesions is absolutely poor or arterial-venous shunt that TACE can not be performed. Known history of human immunodeficiency virus (HIV) infection. Known Central Nervous System tumors including metastatic brain disease. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. History of organ allograft. Known or suspected allergy to the investigational agent or any agent given in association with this trial. Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DEB-TACE plus Sorafenib<br>Patients with unresectable hepatocellular carcinoma (HCC) in this group will receive drug-eluting bead transarterial chemoembolization (DEB-TACE).And then, they will receive sorafenib (400 mg/d, po, bid) one week after DEB-TACE therapy. The second DEB-TACE will be performed after one month later the first DEB-TACE. Lenvatinib will be taken orally for six months, untill tumor progression, or intolerable adverse reactions. | Drug: DEB-TACE plus Sorafenib<br>* Drug-eluting bead transarterial chemoembolization plus sorafenib (400 mg/d, po, bid)<br>|
| Experimental: DEB-TACE plus Lenvatinib<br>Patients with unresectable hepatocellular carcinoma (HCC) in this group will receive drug-eluting bead transarterial chemoembolization (DEB-TACE).And then, they will receive lenvatinib (8 mg/d, po, qd) one week after DEB-TACE therapy. The second DEB-TACE will be performed after one month later the first DEB-TACE. Lenvatinib will be taken orally for six months, untill tumor progression, or intolerable adverse reactions. | Drug: DEB-TACE plus Lenvatinib<br>* Drug-eluting bead transarterial chemoembolization plus lenvatinib (8 mg/d, po, qd)<br>|
| Active Comparator: DEB-TACE plus PD-1 inhibitor<br>Patients with unresectable hepatocellular carcinoma (HCC) in this group will receive drug-eluting bead transarterial chemoembolization (DEB-TACE).And then, they will receive PD-1 inhibitor (200 mg, iv, 3 weeks) one week after DEB-TACE therapy. The second DEB-TACE will be performed after one month later the first DEB-TACE. PD-1 inhibitor will be taken for six months, untill tumor progression, or intolerable adverse reactions. | Drug: DEB-TACE plus PD-1 inhibitor<br>* Drug-eluting bead transarterial chemoembolization plus PD-1 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Primary endpoint is progression-free survival (PFS). | one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival is measured from the date of enrollment until the date of death from any cause. Patients who is lost to follow-up are censored at the last date they are known to be alive, and patients who remain alive are censored at the time of data cutoff. | one month |