Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma

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

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) .

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.

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.