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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01232296
First received: September 30, 2010
Last updated: November 2, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Hepatocellular Carcinoma
Drug: dovitinib
Drug: sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall Survival - Overall Survival [ 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. ] [ Designated as safety issue: Yes ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: Yes ]
    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 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 1 day 1, week 4 day 5 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 1 day 1, week 4 day 5 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 1 day 1, week 4 day 5 ] [ Designated as safety issue: Yes ]
    The mean AUC from time zero to the last measurable concentration sampling time (t last) (mass x time x volume-1)


Enrollment: 162
Study Start Date: July 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TKI258
capsule
Drug: dovitinib
500 mg p.o. o.d. 5 days on/2 days off
Other Name: TKI258
Experimental: Sorafenib
tablet
Drug: sorafenib
400 mg p.o. b.i.d.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232296

Locations
China, Jiangsu
Novartis Investigative Site
Nanjing, Jiangsu, China, 210002
China, Shanxi
Novartis Investigative Site
Xi'an, Shanxi, China, 710032
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310016
China
Novartis Investigative Site
Beijing, China, 100039
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Shatin, New Territories, Hong Kong
Japan
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277-8577
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 232-0024
Novartis Investigative Site
OsakaSayama, Osaka, Japan, 589-8511
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03722
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 05505
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 06351
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Seoul, Korea, Republic of, 136-705
Singapore
Novartis Investigative Site
Singapore, Singapore, 308433
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan, 33305
Novartis Investigative Site
Taichung, Taiwan, 40705
Novartis Investigative Site
Taipei, Taiwan, 10048
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10700
Novartis Investigative Site
Chiang Mai, Thailand, 50200
Novartis Investigative Site
Khon Kaen, Thailand, 40002
Novartis Investigative Site
Songkla, Thailand, 90110
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01232296     History of Changes
Other Study ID Numbers: CTKI258A2208 
Study First Received: September 30, 2010
Results First Received: March 26, 2015
Last Updated: November 2, 2015
Health Authority: United States: Food and Drug Administration
Hong Kong: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Department of Health
Thailand: Food and Drug Administration
Singapore: Health Sciences Authority
China: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Turkey: Ministry of Health

Keywords provided by Novartis:
Hepatocellular Carcinoma
HCC
Liver cancer
Child Pugh A
HCC Stage C

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 26, 2016