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

Phase 2

Completed

Conditions: Hepatocellular Carcinoma

Interventions: Drug: sorafenib
Drug: dovitinib

Registration Number: NCT01232296

Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 162

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sorafenib	sorafenib	tablet
TKI258	dovitinib	capsule

Primary Outcome Measures

Name	Time	Method
Overall Survival - Overall Survival	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.	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

Secondary Outcome Measures

Name	Time	Method
Time to Tumor Progression (Tumor Assessment)	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.	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.
Time to Definitive Deterioration in ECOG Performance Status (PS)	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	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.
Pharmacokinetic (PK) Parameter of Tmax Following a Single Dose of TKI258	Week 1 day 1, week 4 day 5	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)
Pharmacokinetic (PK) Parameter of AUCtau Following a Single Dose of TKI258	Week 1 day 1, week 4 day 5	The mean AUC from time zero to the last measurable concentration sampling time (t last) (mass x time x volume-1)
Disease Control Rate (Tumor Assessment)	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.	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.
Pharmacokinetic (PK) Parameter of Cmax Following a Single Dose of TKI258	Week 1 day 1, week 4 day 5	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).