Clinical trial NCT02229071: Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma
Official title: Donafenib in Advanced Hepatocellular Carcinoma: A Randomized Phase 1B Study of Safety, Efficacy, and Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HCC
Keywords: Donafenib
HCC
Advanced
inoperable
Phase 1B
Lead sponsor: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2014-08-29
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 1 years
Secondary outcomes:
measure: Time to progression(TTP)
timeFrame: 1 year
Other outcomes:
measure: Time to symptomatic progression(TTSP)
timeFrame: 1 year
Locations:
city: Chengdu
country: China
facility: West China Hospital,SCU
state: Sichuan
Study officials:
affiliation: Sichuan University
name: Feng Bi, Doctor
role: PRINCIPAL_INVESTIGATOR
References: