Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This phase IB study of donafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, is to assess toxicity,efficacy and pharmacokinetics in patients wiht advanced hepatocellular carcinoma (HCC) .

Detailed Description
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Eligibility Criteria: 18 -70 years old; Patients with measurable, histologically proven, inoperable HCC; Child-Pugh (CP) score of A; Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients received prior systemic treatments for HCC before 4 weeks; Patients received operate before 3 months; Patients received TACE before 4 weeks; Life expectancy at least 3 months; Adequate hepatic and renal function; Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per deciliter); Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or APTT≤43s;or TT≤21s. Exclusion Criteria: Patients had prior treatment with sorafenib; CNS involvement. Method: open-label,randomized,multiceters study; 2 dose cohorts: 200mg bid and 300mg bid; Patients with advanced HCC(inoperable) and Child-Pugh (CP) A , randomized,receive continuous donafenib either 200mg bid or 300mg bid in 4 weeks cycles; Sample size:106 patients(53 patients in each dose cohort). Endpoints: Safety: toxicities are assessed according to CTCAE 3.0; TTP:Tumor response is assessed every two cycles using RECISIT1.1 criteria; Donafenib pharmacokinetics is measured in plasma samples.

Official Title
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Donafenib in Advanced Hepatocellular Carcinoma: A Randomized Phase 1B Study of Safety, Efficacy, and Pharmacokinetics

Conditions
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HCC

Intervention / Treatment
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* Drug: Donafenib(200mg)
* Drug: Donafenib(300mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 -70 years old Patients with measurable, histologically proven, inoperable HCC Child-Pugh (CP) score of A Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less. Patients received prior systemic treatments for HCC before 4 weeks Patients received operate before 3 months Patients received TACE before 4 weeks Life expectancy at least 3 months Adequate hepatic and renal function Adequate hematologic function (platelet count,≥70×109per liter;hemoglobin ≥8.5 g per deciliter) Prothrombin time international normalized ratio≤2; or prothrombin time ≤16 seconds;or APTT≤43s;or TT≤21s. Exclusion Criteria: Patients had prior treatment with sorafenib CNS involvement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Donafenib(200mg)<br>Donafenib 200 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. | Drug: Donafenib(200mg)<br>* Donafenib 200mg,bid,po<br>* Other names: A Group;|
| Active Comparator: Donafenib(300mg)<br>Donafenib 300 mg orally twice daily,each 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops. | Drug: Donafenib(300mg)<br>* Donafenib 300mg,bid,po<br>* Other names: B Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Patient visits are scheduled every 4 weeks to monitor safety and drug accountability. Patients were monitored for adverse events by use of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0 | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression(TTP) | Patient visits are scheduled every 8 weeks to monitor efficacy.TTP is measured from the date of randomisation until disease progression according to RECIST 1.1. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donafenib, HCC, Advanced, inoperable, Phase 1B