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

Primary Purpose

Advanced Hepatocellular Carcinoma

Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
INC280
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma focused on measuring INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Massachusetts General Hospital Mass General Hospital
  • Research Medical Center Onc Dept
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

INC280 plus best supportive care

Placebo plus best supportive care

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
Safety: adverse events, serious adverse events
Frequency, duration and severity of adverse events.
Safety: hematology and chemistry values, vital signs, electrocardiograms
Change from baseline values.
Tolerability of study drug
Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.

Full Information

First Posted
October 14, 2013
Last Updated
August 30, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01964235
Brief Title
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

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Withdrawn
Why Stopped
Study was cancelled by Sponsor.
Study Start Date
December 2016 (undefined)
Primary Completion Date
July 2019 (Anticipated)
Study Completion Date
July 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma
Keywords
INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
INC280 plus best supportive care
Arm Type
Experimental
Arm Description
Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.
Arm Title
Placebo plus best supportive care
Arm Type
Placebo Comparator
Arm Description
Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.
Intervention Type
Drug
Intervention Name(s)
INC280
Intervention Description
INC280 will be administered orally and continuously on a twice a day dosing schedule.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered orally and continuously on a twice a day dosing schedule.
Primary Outcome Measure Information:
Title
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Description
Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression.
Time Frame
baseline, 6 weeks up to 6 months
Secondary Outcome Measure Information:
Title
Best Overall Response
Description
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.
Time Frame
date of treatment, every 6 weeks up to 6 months
Title
Overall Response Rate
Description
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.
Time Frame
baseline, every 6 weeks up to 6 months
Title
Disease Control Rate
Description
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.
Time Frame
baseline, every 6 weeks up to 6 months
Title
Progression Free Survival
Description
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.
Time Frame
randomization, every 6 weeks up to 6 months
Title
Overall Survival
Description
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.
Time Frame
randomization until death, average 10 months
Title
Safety: adverse events, serious adverse events
Description
Frequency, duration and severity of adverse events.
Time Frame
From baseline until 30 days post study treatment
Title
Safety: hematology and chemistry values, vital signs, electrocardiograms
Description
Change from baseline values.
Time Frame
From baseline until end of treatment, average 6 months from baseline
Title
Tolerability of study drug
Description
Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.
Time Frame
From date of randomization until end of treatment, average 6 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Massachusetts General Hospital Mass General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Research Medical Center Onc Dept
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64132
Country
United States
Facility Name
Novartis Investigative Site
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Novartis Investigative Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Novartis Investigative Site
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Novartis Investigative Site
City
LILLE Cedex
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Novartis Investigative Site
City
Nice Cedex 3
ZIP/Postal Code
06202
Country
France
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong SAR
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Cordoba
State/Province
Andalucia
ZIP/Postal Code
14004
Country
Spain
Facility Name
Novartis Investigative Site
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Genève
ZIP/Postal Code
1211
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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