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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: dovitinib
* Drug: sorafenib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TKI258<br>capsule | Drug: dovitinib<br>* 500 mg p.o. o.d. 5 days on/2 days off<br>* Other names: TKI258;|
| Experimental: Sorafenib<br>tablet | Drug: sorafenib<br>* 400 mg p.o. b.i.d.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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. | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, HCC, Liver cancer, Child Pugh A, HCC Stage C