Donafenib and Toripalimab Combined With TACE in Patients With Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This study is the single-center, open-label phase I clinical trial to evaluate tolerability, safety and efficacy of Donafenib and JS001 in combination with TCAE in patients with Unresectable Hepatocellular Carcinoma.

Detailed Description
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The phase I clinical trial is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Donafenib in this regimen, and select an acceptable safe dose for the phase II clinical trial(RP2D).

Official Title
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Dose Escalation Study Of Donafenib and Toripalimab Combined With TACE in Patients With Unresectable Hepatocellular Carcinoma

Conditions
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Unresectable Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Donafenib Tosilate Tablets
* Biological: Toripalimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 (inclusive), male or female; Diagnosis of Unresectable Hepatocellular Carcinoma confirmed clinically or histologically or cytologically according to the Guidelines for diagnosis and treatment of primary liver cancer (2019 Edition); At least one measurable lesion (according to RECIST v1.1) ECOG performance status score of 0 -1; Life expectancy ≥ 12 weeks; Fully understand this research and voluntarily sign the ICF. Exclusion Criteria: Diffuse liver cancer； Refractory hepatic encephalopathy, refractory ascites, or hepatorenal syndrome； Pregnancy or lactation； Patients with extrahepatic diffusion； Spontaneous tumor rupture； Expected non-compliance.

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donafenib/JS001/TACE<br>Donafenib and JS001 Combined With TACE | Drug: Donafenib Tosilate Tablets<br>* 100mg Qd/150mg Qd/100mg Bid, po<br>Biological: Toripalimab Injection<br>* 240 mg, iv drip,q3w<br>* Other names: JS001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity(DLT) | Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity. | 21 days after the first dose of JS001 and Donafenib, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date. | From the date of randomization until death due to any cause, assessed up to 2 years. | 
| Progression free survival (PFS) | The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented progression or date of death | From date of randomization until the date of objective disease progression or death, assessed up to 2 years. | 
| Duration of response (DOR) | defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death | From the date of first documented response (RECIST 1.1.) until the first date of documented progression or death in the absence of disease progression, assessed up to 2 years. |