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

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

dovitinib

sorafenib

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, HCC, Liver cancer, Child Pugh A, HCC Stage C

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

TKI258

Sorafenib

Arm Description

capsule

tablet

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

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.

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).

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)

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)

Full Information

NCT ID

NCT01232296

First Posted

September 30, 2010

Last Updated

November 2, 2015

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01232296

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

April 2014 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma, HCC, Liver cancer, Child Pugh A, HCC Stage C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

162 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TKI258

Arm Type

Experimental

Arm Description

capsule

Arm Title

Sorafenib

Arm Type

Experimental

Arm Description

tablet

Intervention Type

Drug

Intervention Name(s)

dovitinib

Other Intervention Name(s)

TKI258

Intervention Description

500 mg p.o. o.d. 5 days on/2 days off

Intervention Type

Drug

Intervention Name(s)

sorafenib

Intervention Description

400 mg p.o. b.i.d.

Primary Outcome Measure Information:

Title

Overall Survival - Overall Survival

Description

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

Time Frame

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 Measure Information:

Title

Time to Tumor Progression (Tumor Assessment)

Description

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 Frame

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.

Title

Disease Control Rate (Tumor Assessment)

Description

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.

Time Frame

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.

Title

Time to Definitive Deterioration in ECOG Performance Status (PS)

Description

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.

Time Frame

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

Title

Pharmacokinetic (PK) Parameter of Cmax Following a Single Dose of TKI258

Description

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).

Time Frame

Week 1 day 1, week 4 day 5

Title

Pharmacokinetic (PK) Parameter of Tmax Following a Single Dose of TKI258

Description

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)

Time Frame

Week 1 day 1, week 4 day 5

Title

Pharmacokinetic (PK) Parameter of AUCtau Following a Single Dose of TKI258

Description

The mean AUC from time zero to the last measurable concentration sampling time (t last) (mass x time x volume-1)

Time Frame

Week 1 day 1, week 4 day 5

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210002

Country

China

Facility Name

Novartis Investigative Site

City

Xi'an

State/Province

Shanxi

ZIP/Postal Code

710032

Country

China

Facility Name

Novartis Investigative Site

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310016

Country

China

Facility Name

Novartis Investigative Site

City

Beijing

ZIP/Postal Code

100039

Country

China

Facility Name

Novartis Investigative Site

City

Hong Kong

Country

Hong Kong

Facility Name

Novartis Investigative Site

City

Shatin, New Territories

Country

Hong Kong

Facility Name

Novartis Investigative Site

City

Kashiwa

State/Province

Chiba

ZIP/Postal Code

277-8577

Country

Japan

Facility Name

Novartis Investigative Site

City

Yokohama-city

State/Province

Kanagawa

ZIP/Postal Code

232-0024

Country

Japan

Facility Name

Novartis Investigative Site

City

OsakaSayama

State/Province

Osaka

ZIP/Postal Code

589-8511

Country

Japan

Facility Name

Novartis Investigative Site

City

Seoul

State/Province

Korea

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Seoul

State/Province

Korea

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Seoul

State/Province

Korea

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Seoul

State/Province

Korea

ZIP/Postal Code

110 744

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Seoul

ZIP/Postal Code

136-705

Country

Korea, Republic of

Facility Name

Novartis Investigative Site

City

Singapore

ZIP/Postal Code

308433

Country

Singapore

Facility Name

Novartis Investigative Site

City

Taipei

State/Province

Taiwan, ROC

ZIP/Postal Code

112

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Kuei-Shan Chiang

State/Province

Taoyuan/ Taiwan ROC

ZIP/Postal Code

33305

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taichung

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taipei

ZIP/Postal Code

10048

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Novartis Investigative Site

City

Chiang Mai

ZIP/Postal Code

50200

Country

Thailand

Facility Name

Novartis Investigative Site

City

Khon Kaen

ZIP/Postal Code

40002

Country

Thailand

Facility Name

Novartis Investigative Site

City

Songkla

ZIP/Postal Code

90110

Country

Thailand

Hepatocellular Carcinoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial