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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: INC280; Drug: Placebo

Detailed Description

Study was cancelled by Sponsor prior to enrollment of patients.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
• France
  • Clichy, France, 92110
    • Novartis Investigative Site
  • LILLE Cedex, France, 59037
    • Novartis Investigative Site
  • Montpellier Cedex 5, France, 34298
    • Novartis Investigative Site
  • Nice Cedex 3, France, 06202
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Würzburg, Germany, 97080
    • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Hong Kong SAR, Hong Kong
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Genève, Switzerland, 1211
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital Mass General Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center Onc Dept

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INC280 plus best supportive care; Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.	Drug: INC280; INC280 will be administered orally and continuously on a twice a day dosing schedule.
Placebo Comparator: Placebo plus best supportive care; Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.	Drug: Placebo; Placebo will be administered orally and continuously on a twice a day dosing schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Safety: adverse events, serious adverse events	Frequency, duration and severity of adverse events.	From baseline until 30 days post study treatment
Safety: hematology and chemistry values, vital signs, electrocardiograms	Change from baseline values.	From baseline until end of treatment, average 6 months from baseline
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: October 14, 2013
• First Posted (Estimate): October 17, 2013

Study Record Updates

• Last Update Posted (Estimate): September 1, 2016
• Last Update Submitted That Met QC Criteria: August 30, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CINC280X2203