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

Primary Purpose

Advanced Hepatocellular Carcinoma With c-MET Dysregulation

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

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma With c-MET Dysregulation 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.
  • Advanced hepatocellular carcinoma which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy.
  • Measurable disease as determined by RECIST version 1.1.
  • Current cirrhotic status of Child-Pugh class A with no encephalopathy.
  • Eastern Cooperative Oncology Group (ECOG) performance status < or = 2.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Received any prior systemic chemotherapy or molecular-targeted therapy for hepatocellular carcinoma such as sorafenib.
  • Previous treatment with c-MET inhibitor or hepatocyte growth factor targeting therapy.
  • Previous local therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade 1.
  • Known active bleeding (e.g. bleeding from gastro-intestinal ulcers or esophageal varices) within 2 months prior to screening or with history or evidence of inherited bleeding diathesis or coagulopathy.
  • Clinically significant venous or arterial thrombotic disease within past 6 months.
  • History of acute or chronic pancreatitis, surgery of pancreas or any risk factors that may increase risk of pancreatitis.
  • Other protocol-defined exclusion criteria may apply.

Sites / Locations

  • 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 Type

Experimental

Arm Label

INC280

Arm Description

The protocol consists of two independent parts (Dose-Determining Part and Dose Expansion Part). Approximately 6 patients will be treated with INC280 300 mg twice a day in the Dose-Determining Part. Approximately 50 patients will be treated with INC280 in the Dose Expansion Part. The dose for the Expansion Part can be lower, equal or higher than in the Dose-Determining Part will be determined after the Dose Determining Part at the dose decision analysis.

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 or death due to underlying cancer.

Secondary Outcome Measures

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.
Progression free survival
Progression free survival is defined as the time from date of first study treatment intake to the date of the first radiologically documented progression or death due to any cause or initiation of new antineoplastic therapy. if a patient has not had an event, 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 first study treatment intake 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.
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
Safety: adverse events, serious adverse events
Frequency and severity of adverse events.
Number of participants with dose interruptions and dose reductions
Number of participants with at least one dose interruption of INC280 and number of participants with at least one dose reduction of INC280.
Dose intensity
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.
Plasma pharmacokinetic parameter: AUC0-t
Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve
Plasma pharmacokinetic parameter: CL/F
Plasma concentration of INC280 versus time profiles
Plasma pharmacokinetic parameter: Cmax
Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration
Plasma pharmacokinetic parameter: Tmax
Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration
Plasma pharmacokinetic parameter: T1/2
Plasma concentration of INC280 versus time profiles
Plasma pharmacokinetic parameter: Racc
Plasma concentration of INC280 versus time profiles

Full Information

First Posted
November 12, 2012
Last Updated
July 4, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01737827
Brief Title
Study Efficacy and Safety of INC280 in Patients With Advanced Hepatocellular Carcinoma.
Official Title
A Phase II, Open Label, Single Arm, Multicenter Study of INC280 Administered Orally in Adults With Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Terminated
Why Stopped
The study recruitment was ended due to difficulties in identifying subjects who meet the eligibility criteria and therefore the study never reached its planned sample size per protocol. The study termination was not due to any safety concerns.
Study Start Date
March 25, 2013 (Actual)
Primary Completion Date
April 24, 2023 (Actual)
Study Completion Date
May 24, 2023 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is to find out if INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway.
Detailed Description
This study is designed as a Phase II, single arm, open-label, multicenter study to evaluate the safety and efficacy of INC280 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for or had disease progression after surgical or locoregional therapies, with c- MET dysregulation. The study includes a Dose-Determining Part and a Dose Expansion Part. Pharmacokinetic and safety profiles of INC280 in the setting of liver dysfunction will be determined in the Dose-Determining Part. The Dose Expansion Part will start when the appropriate dose for patients with liver dysfunction is determined based on pharmacokinetics (PK) and safety data from the Dose-Determining Part and other INC280 ongoing clinical studies.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
INC280
Arm Type
Experimental
Arm Description
The protocol consists of two independent parts (Dose-Determining Part and Dose Expansion Part). Approximately 6 patients will be treated with INC280 300 mg twice a day in the Dose-Determining Part. Approximately 50 patients will be treated with INC280 in the Dose Expansion Part. The dose for the Expansion Part can be lower, equal or higher than in the Dose-Determining Part will be determined after the Dose Determining Part at the dose decision analysis.
Intervention Type
Drug
Intervention Name(s)
INC280
Intervention Description
INC280 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 or death due to underlying cancer.
Time Frame
Average of 6 weeks, up to 8 years
Secondary Outcome Measure Information:
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
Average of 6 weeks, up to 8 years
Title
Progression free survival
Description
Progression free survival is defined as the time from date of first study treatment intake to the date of the first radiologically documented progression or death due to any cause or initiation of new antineoplastic therapy. if a patient has not had an event, progression free survival is censored at the date of last adequate tumor assessment.
Time Frame
Average of 6 weeks, up to 8 years
Title
Overall survival
Description
Overall survival is defined as the time from date of first study treatment intake 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
Average of 6 weeks, up to 8 years
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
Average of 6 weeks, up to 8 years
Title
Safety: adverse events, serious adverse events
Description
Frequency and severity of adverse events.
Time Frame
Average of 6 weeks, up to 8 years
Title
Number of participants with dose interruptions and dose reductions
Description
Number of participants with at least one dose interruption of INC280 and number of participants with at least one dose reduction of INC280.
Time Frame
Average of 6 weeks, up to 8 years
Title
Dose intensity
Description
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.
Time Frame
Average of 6 weeks, up to 8 years
Title
Plasma pharmacokinetic parameter: AUC0-t
Description
Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Title
Plasma pharmacokinetic parameter: CL/F
Description
Plasma concentration of INC280 versus time profiles
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Title
Plasma pharmacokinetic parameter: Cmax
Description
Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Title
Plasma pharmacokinetic parameter: Tmax
Description
Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Title
Plasma pharmacokinetic parameter: T1/2
Description
Plasma concentration of INC280 versus time profiles
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Title
Plasma pharmacokinetic parameter: Racc
Description
Plasma concentration of INC280 versus time profiles
Time Frame
Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed c-MET pathway dysregulation. Advanced hepatocellular carcinoma which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy. Measurable disease as determined by RECIST version 1.1. Current cirrhotic status of Child-Pugh class A with no encephalopathy. Eastern Cooperative Oncology Group (ECOG) performance status < or = 2. Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Received any prior systemic chemotherapy or molecular-targeted therapy for hepatocellular carcinoma such as sorafenib. Previous treatment with c-MET inhibitor or hepatocyte growth factor targeting therapy. Previous local therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade 1. Known active bleeding (e.g. bleeding from gastro-intestinal ulcers or esophageal varices) within 2 months prior to screening or with history or evidence of inherited bleeding diathesis or coagulopathy. Clinically significant venous or arterial thrombotic disease within past 6 months. History of acute or chronic pancreatitis, surgery of pancreas or any risk factors that may increase risk of pancreatitis. Other protocol-defined exclusion criteria may apply.
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
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210002
Country
China
Facility Name
Novartis Investigative Site
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310016
Country
China
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
168583
Country
Singapore
Facility Name
Novartis Investigative Site
City
Khon Kaen
State/Province
THA
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Citations:
PubMed Identifier
31853265
Citation
Qin S, Chan SL, Sukeepaisarnjaroen W, Han G, Choo SP, Sriuranpong V, Pan H, Yau T, Guo Y, Chen M, Ren Z, Xu J, Yen CJ, Lin ZZ, Manenti L, Gu Y, Sun Y, Tiedt R, Hao L, Song W, Tanwandee T. A phase II study of the efficacy and safety of the MET inhibitor capmatinib (INC280) in patients with advanced hepatocellular carcinoma. Ther Adv Med Oncol. 2019 Dec 11;11:1758835919889001. doi: 10.1177/1758835919889001. eCollection 2019. Erratum In: Ther Adv Med Oncol. 2020 Mar 12;12:1758835920913426.
Results Reference
derived

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

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