A Study of Dovitinib Versus Sorafenib in Adult Patients With Hepatocellular Carcinoma (HCC) as a First Line Treatment

Hepatocellular Carcinoma Clinical Trial

Official title:

An Open-label, Randomized, Multi-center, Phase II Study to Compare the Safety and Efficacy of TKI258 Versus Sorafenib as First-line Treatment in Adult Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01232296
• Other study ID #: CTKI258A2208
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2010
• Last updated: November 2, 2015
• Start date: July 2011
• Est. completion date: April 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationHong Kong: Department of HealthSouth Korea: Korea Food and Drug Administration (KFDA)Taiwan: Department of HealthThailand: Food and Drug AdministrationSingapore: Health Sciences AuthorityChina: Food and Drug AdministrationJapan: Pharmaceuticals and Medical Devices AgencyTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this open-label, randomized, phase II study is to compare the safety and efficacy of dovitinib versus sorafenib as first-line treatment in adult patients with advanced Hepatocellular Carcinoma (HCC). This trial will be opened in countries of the Asia-Pacific region.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 162
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Diagnosis of advanced Hepatocellular Carcinoma (HCC) according to the AASLD Guidelines

• Advance HCC Stage B and C according to BCLC staging classification

• Child Pugh A

• At least one measurable lesion as assessed by CT or MRI

• ECOG PS of 0 or 1

• Adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Prior systemic therapy for HCC

• Brain metastases

• Active bleeding (including variceal bleeding as the result of esophageal varices) Patients who have received a liver transplant or are awaiting an immediate transplant

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• dovitinib
500 mg p.o. o.d. 5 days on/2 days off
• sorafenib
400 mg p.o. b.i.d.

Locations

Country	Name	City	State
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Xi'an	Shanxi
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	OsakaSayama	Osaka
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Kuei-Shan Chiang	Taoyuan/ Taiwan ROC
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen
Thailand	Novartis Investigative Site	Songkla

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

China,  Hong Kong,  Japan,  Korea, Republic of,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival - Overall Survival	The overall survival (OS), defined as the time from date of randomization to the date of death from any cause. If a patient was not known to have died at the date of analysis cut-off, OS was censored at the last date of contact. Survival information was collected every 6 wks until at least 130 deaths have been observed	Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.	Yes
Secondary	Time to Tumor Progression (Tumor Assessment)	Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). For target lesions, disease progression mean at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, disease progression refers to unequivocal progression of existing non-target lesions. In addition, the appearance of new lesions is always considered as disease progression.	Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.	No
Secondary	Disease Control Rate (Tumor Assessment)	Disease Control Rate (DCR) is defined as the proportion of patients whose best overall response is either complete response [CR], partial response [PR] or stable disease [SD] according to RECIST 1.1.	Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first.	Yes
Secondary	Time to Definitive Deterioration in ECOG Performance Status (PS)	Time to definitive deterioration on ECOG PS scale (by at least one point) was defined as the time from the date of randomization to the date of definitive deterioration of the ECOG PS by at least one category of the score from baseline or to the date of death whichever occurred earlier. 0 is Fully active, able to carry on all pre-disease performance without restriction, 1 is Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work and 2 is ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.	Every 6 weeks from date of randomization until the patient has progressed, or the patient can no longer be followed, or at least 130 deaths have been observed in the study, whichever came first	No
Secondary	Pharmacokinetic (PK) Parameter of Cmax Following a Single Dose of TKI258	Cmax will be evaluated after a single dose of TKI258 following a 5 days on/2 days off dosing schedule. Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after a single dose administration (mass x volume - 1).	Week 1 day 1, week 4 day 5	Yes
Secondary	Pharmacokinetic (PK) Parameter of Tmax Following a Single Dose of TKI258	Tmax will be evaluated after a single dose of TKI258 following a 5 days on/2 days off dosing schedule. Tmax is the time to to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after a single dose administration (time)	Week 1 day 1, week 4 day 5	Yes
Secondary	Pharmacokinetic (PK) Parameter of AUCtau Following a Single Dose of TKI258	The mean AUC from time zero to the last measurable concentration sampling time (t last) (mass x time x volume-1)	Week 1 day 1, week 4 day 5	Yes