Safety and Efficacy of Donafenib in Patients With Advanced Hepatocellular Carcinoma

HCC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02229071
• Other study ID #: ZGDH1B
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2014
• Est. completion date: October 30, 2016

Study information

• Verified date: March 2015
• Source: Suzhou Zelgen Biopharmaceuticals Co.,Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) .

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: October 30, 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• HCC

Intervention

Drug:
• Donafenib(200mg)
Donafenib 200mg,bid,po
• Donafenib(300mg)
Donafenib 300mg,bid,po

Locations

Country	Name	City	State
China	West China Hospital,SCU	Chengdu	Sichuan

Sponsors (2)

Lead Sponsor	Collaborator
Suzhou Zelgen Biopharmaceuticals Co.,Ltd	Tigermed Consulting Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to symptomatic progression(TTSP)	Symtomatic progression is measured with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-HP) domain of physical wellbeing and additional concerns at baseline and every 4 weeks.TTSP is measured from the date of randomisation until symptomatic progression.	1 year
Primary	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	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