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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01964235




Registration number
NCT01964235
Ethics application status
Date submitted
14/10/2013
Date registered
17/10/2013
Date last updated
1/09/2016

Titles & IDs
Public title
Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma
Scientific title
A Randomized Phase II, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of INC280 in Adult Patients With Advanced Hepatocellular Carcinoma After Progression or Intolerance to Sorafenib Treatment
Secondary ID [1] 0 0
CINC280X2203
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INC280
Treatment: Drugs - Placebo

Experimental: INC280 plus best supportive care - Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.

Placebo Comparator: Placebo plus best supportive care - Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.


Treatment: Drugs: INC280
INC280 will be administered orally and continuously on a twice a day dosing schedule.

Treatment: Drugs: Placebo
Placebo will be administered orally and continuously on a twice a day dosing schedule.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Timepoint [1] 0 0
baseline, 6 weeks up to 6 months
Secondary outcome [1] 0 0
Best Overall Response
Timepoint [1] 0 0
date of treatment, every 6 weeks up to 6 months
Secondary outcome [2] 0 0
Overall Response Rate
Timepoint [2] 0 0
baseline, every 6 weeks up to 6 months
Secondary outcome [3] 0 0
Disease Control Rate
Timepoint [3] 0 0
baseline, every 6 weeks up to 6 months
Secondary outcome [4] 0 0
Progression Free Survival
Timepoint [4] 0 0
randomization, every 6 weeks up to 6 months
Secondary outcome [5] 0 0
Overall Survival
Timepoint [5] 0 0
randomization until death, average 10 months
Secondary outcome [6] 0 0
Safety: adverse events, serious adverse events
Timepoint [6] 0 0
From baseline until 30 days post study treatment
Secondary outcome [7] 0 0
Safety: hematology and chemistry values, vital signs, electrocardiograms
Timepoint [7] 0 0
From baseline until end of treatment, average 6 months from baseline
Secondary outcome [8] 0 0
Tolerability of study drug
Timepoint [8] 0 0
From date of randomization until end of treatment, average 6 months from baseline

Eligibility
Key inclusion criteria
- Confirmed c-MET pathway dysregulation.- Hepatocellular carcinoma stage B or C
according to the Barcelona Clinic Liver cancer staging classification. - Current
cirrhotic status of Child-Pugh class A with no encephalopathy. - Documented disease
progression during or after discontinuation of sorafenib treatment or intolerance to
sorafenib treatment. - Measurable disease as determined by RECIST v1.1. - ECOG
performance status = 1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous local antineoplastic therapy or investigational drug completed less than 5
half-lives of the agent prior to randomization and have not recovered from clinically
significant toxicity from such treatment to grade =1 by the NCI-CTCAE. - Received any
targeted therapy other than sorafenib.

- Active bleeding within 28 days prior to screening visit including variceal bleeding
(esophageal varices should be treated according to standard practice and procedure
completed 28 days prior to screening visit). - Clinically significant venous or
arterial thrombotic disease within past 6 months.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/12/2016
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2019
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kogarah
Recruitment hospital [2] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
France
State/province [3] 0 0
Clichy
Country [4] 0 0
France
State/province [4] 0 0
LILLE Cedex
Country [5] 0 0
France
State/province [5] 0 0
Montpellier Cedex 5
Country [6] 0 0
France
State/province [6] 0 0
Nice Cedex 3
Country [7] 0 0
Germany
State/province [7] 0 0
Essen
Country [8] 0 0
Germany
State/province [8] 0 0
Würzburg
Country [9] 0 0
Hong Kong
State/province [9] 0 0
Hong Kong SAR
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Hong Kong
Country [11] 0 0
Spain
State/province [11] 0 0
Andalucia
Country [12] 0 0
Switzerland
State/province [12] 0 0
Bern
Country [13] 0 0
Switzerland
State/province [13] 0 0
Genève

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study is establish whether INC280 is safe and has beneficial effects in patients with
advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway and whose
disease progressed while on, or after, treatment with sorafenib or who are intolerant to
sorafenib.

Patients will be randomized in a 2:1 ratio to receive INC280 at 600mg BID plus best
supportive care (BSC) or placebo plus BSC, until disease progression or intolerable to study
treatment. Patients treated with placebo plus BSC will have the opportunity to receive INC280
treatment upon documented further disease progression (RECIST 1.1) per investigator's
discretion after unblinding.

Patient will be stratified to geographical region (Asia vs Rest of World ) and tumor burden
(present macroscopic vascular invasion and/or extra-hepatic spread vs not present).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01964235
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01964235