Clinical trial NCT01964235: Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma
Official 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Advanced Hepatocellular Carcinoma
Keywords: INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-10-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: Study was cancelled by Sponsor prior to enrollment of patients.

Eligibility criteria: 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

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.

Primary outcomes:
measure: Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
timeFrame: baseline, 6 weeks up to 6 months
Secondary outcomes:
measure: Best Overall Response
timeFrame: date of treatment, every 6 weeks up to 6 months
measure: Overall Response Rate
timeFrame: baseline, every 6 weeks up to 6 months
measure: Disease Control Rate
timeFrame: baseline, every 6 weeks up to 6 months
measure: Progression Free Survival
timeFrame: randomization, every 6 weeks up to 6 months
measure: Overall Survival
timeFrame: randomization until death, average 10 months
measure: Safety: adverse events, serious adverse events
timeFrame: From baseline until 30 days post study treatment
measure: Safety: hematology and chemistry values, vital signs, electrocardiograms
timeFrame: From baseline until end of treatment, average 6 months from baseline
measure: Tolerability of study drug
timeFrame: From date of randomization until end of treatment, average 6 months from baseline
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Mass General Hospital
state: Massachusetts
city: Kansas City
country: United States
facility: Research Medical Center Onc Dept
state: Missouri
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Clichy
country: France
facility: Novartis Investigative Site
city: LILLE Cedex
country: France
facility: Novartis Investigative Site
city: Montpellier Cedex 5
country: France
facility: Novartis Investigative Site
city: Nice Cedex 3
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Hong Kong SAR
country: Hong Kong
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Genève
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: