cTACE or DEB-TACE+HAIC Combined With Regorafenib ± Anti-PD1 Antibody for uHCC

Study Overview
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Brief Summary
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explore the effectiveness and safety of conventional transarterial chemoembolization (cTACE) or transarterial chemoembolization (DEB-TACE) plus hepatic arterial Infusion chemotherapy (HAIC) combined with regorafenib and anti-PD-1 antibody or not for unresected hepatocellular carcinoma (uHCC)

Detailed Description
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This is a non-randomized, open, single-arm clinical study. Patients receive cTACE/DEB-TACE+HAIC treatment( 6-8 weeks as a cycle) and regorafenib and anti-PD1 antibody or not until the disease progresses, intolerable toxicity occurs, the patient is lost to follow-up or death, or situations other judged by researchers which treatment should be stopped.

Official Title
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Conventional Transarterial Chemoembolization (cTACE) or Transarterial Chemoembolization (DEB-TACE) +HAIC Combined With Regorafenib ± Anti-PD1 Antibody for Unresected Hepatocellular Carcinoma

Conditions
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HCC, Transarterial Chemoembolization, Hepatic Arterial Infusion Chemotherapy, Regorafenib

Intervention / Treatment
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* Drug: Regorafenib
* Device: cTACE/DEB-TACE-HAIC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate and sign the informed consent in writing; Age: 18-75 years old; No gender limit; Unresectable hepatocellular carcinoma with clear pathological diagnosis or clinical diagnosis; Unresectable hepatocellular carcinoma patients who failed first-line treatment (including but not limited to sorafenib, lenvatinib, atezolizumab combined with bevacizumab, etc.); At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection; Child-pugh grade A-B7 grade The expected survival period is ≥3 months; General physical condition (ECOG) 0-2; Sufficient bone marrow hematopoietic function (within 7 days): hemoglobin ≥9 g/dL, white blood cells ≥3.0×10^9/L, neutrophils ≥1.5x 10^9/L, platelets ≥80x 10^9/L; liver and kidney functions are normal; (Within 14 days): TBIL≤1.5 times the upper limit of normal; ALT and AST≤5 times the upper limit of normal; creatinine≤1.5 times the upper limit of normal; INR≤1.7 or prolonged PT≤4s. Exclusion Criteria: Those who are currently receiving other effective treatments; Patients who have received regorafenib in the past; Patients who have participated in other clinical trials within 4 weeks before enrollment; Unable to cooperate with cTACE and HAIC treatment; Patients with primary malignant tumors other than hepatocellular carcinoma at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ; Clinically significant cardiovascular diseases, such as heart failure (NYHA III-IV), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or a history of myocardial infarction within the past 1 year; Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer; There were active serious clinical infections (>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment; Known or self-reported HIV infection; Uncontrolled systemic diseases, such as poorly controlled diabetes; Known to have hypersensitivity or allergic reactions to any component of the study drug; Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cTACE/DEB-TACE-HAIC+regorafenib±anti-PD1 antibody<br>patients will receive the combination treatment of cTACE/DEB-TACE plus HAIC and combined with regorafenib and anti-PD1 antibody or not. The anti-PD-1 antibody will be used depended on the contraindications or wishes of patients. | Drug: Regorafenib<br>* patients will received TACE-HAIC and regorafenib and anti-PD1 antibody or not<br>* Other names: anti-PD1 antibody;Device: cTACE/DEB-TACE-HAIC<br>* conventional transarterial chemoembolization(cTACE)/transarterial chemoembolization (DEB-TACE) plus hepatic artery infusion<br>* Other names: conventional transarterial chemoembolization(cTACE)/transarterial chemoembolization (DEB-TACE) plus hepatic artery infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate, ORR | The objective response rate (ORR) was defined as the complete response (CR) rate + the partial response (PR) rate | 6 months | 
| Progression free overall survival，PFS | PFS was defined as the interval between the time at which treatment was initiated and intrahepatic tumor and/or extrahepatic tumor progression, symptomatic progression, including massive ascites and liver function that was categorized as Child-Pugh grade C, or death from any cause | 12 months | 
| Overall survival，OS | overall survival (OS) was defined as the interval between the time at which treatment was initiated and death or the last follow-up assessment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate, DCR | disease control rate (DCR) was defined as the CR rate + the PR rate + the stable disease (SD) rate | 6 months |