Study of Efficacy and Safety INC280 in Patients With Advanced Hepatocellular Carcinoma

Advanced Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01964235
• Other study ID #: CINC280X2203
• Status: Withdrawn
• Phase: Phase 2
• First received: October 14, 2013
• Last updated: August 30, 2016
• Start date: December 2016
• Est. completion date: July 2019

Study information

• Verified date: August 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: Agencia Española de Medicamentos y Productos SanitariosAustria: Agency for Health and Food SafetyHong Kong: Department of HealthKorea: Ministry for Health and WelfareAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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).

Description:

Study was cancelled by Sponsor prior to enrollment of patients.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• INC280
INC280 will be administered orally and continuously on a twice a day dosing schedule.
• Placebo
Placebo will be administered orally and continuously on a twice a day dosing schedule.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Kogarah	New South Wales
France	Novartis Investigative Site	Clichy
France	Novartis Investigative Site	LILLE Cedex
France	Novartis Investigative Site	Montpellier Cedex 5
France	Novartis Investigative Site	Nice Cedex 3
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Würzburg
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Hong Kong SAR
Spain	Novartis Investigative Site	Cordoba	Andalucia
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Genève
United States	Massachusetts General Hospital Mass General Hospital	Boston	Massachusetts
United States	Research Medical Center Onc Dept	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Hong Kong,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1	Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression.	baseline, 6 weeks up to 6 months	No
Secondary	Best Overall Response	Best overall response is defined as the best response recorded from the date of randomization until the date of last tumor assessment per RECIST version 1.1.	date of treatment, every 6 weeks up to 6 months	No
Secondary	Overall Response Rate	Overall Response Rate is defined as the proportion of patients with a best overall response of complete response or partial response at any time on study per RECIST version 1.1.	baseline, every 6 weeks up to 6 months	No
Secondary	Disease Control Rate	Disease control rate is defined as the proportion of patients with a best overall response of complete response, partial response or stable disease at any time on study per RECIST version 1.1.	baseline, every 6 weeks up to 6 months	No
Secondary	Progression Free Survival	Progression free survival is defined as the time from date of randomization to the date of the first radiologically documented progression or death due to any cause. If a patient has not experienced radiologically documented progression or death, progression free survival is censored at the date of last adequate tumor assessment.	randomization, every 6 weeks up to 6 months	No
Secondary	Overall Survival	Overall survival is defined as the time from date of randomization to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.	randomization until death, average 10 months	No
Secondary	Safety: adverse events, serious adverse events	Frequency, duration and severity of adverse events.	From baseline until 30 days post study treatment	Yes
Secondary	Safety: hematology and chemistry values, vital signs, electrocardiograms	Change from baseline values.	From baseline until end of treatment, average 6 months from baseline	Yes
Secondary	Tolerability of study drug	Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.	From date of randomization until end of treatment, average 6 months from baseline	Yes