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

NCT01737827

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CINC280X2201
  • NCT ID: NCT01737827

Conditions

  • Advanced Hepatocellular Carcinoma With c-MET Dysregulation

Interventions

DrugSynonymsArms
INC280INC280

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
INC280ExperimentalThe 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.
  • INC280

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time Frame:baseline, 6 weeks up to 6 months
Safety Issue:
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.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:baseline, every 6 weeks up to 6 months
Safety Issue:
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.
Measure:Progression free survival
Time Frame:date of treatment, every 6 weeks up to 6 months
Safety Issue:
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.
Measure:Overall survival
Time Frame:From date of treatment until death, average 10.7 months
Safety Issue:
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.
Measure:Disease Control Rate
Time Frame:baseline, every 6 weeks up to 6 months
Safety Issue:
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
Measure:Safety: adverse events, serious adverse events
Time Frame:From baseline until 30 days post study treatment
Safety Issue:
Description:Frequency, duration and severity of adverse events.
Measure:Safety: hematology and chemistry values, vital signs, electrocardiograms
Time Frame:From baseline until end of treatment, average 6 months from baseline
Safety Issue:
Description:Change from baseline values.
Measure:Tolerability of study drug
Time Frame:From date start of treatment until end of treatment, average 6 months from baseline
Safety Issue:
Description:Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity.
Measure:Plasma pharmacokinetic parameter: AUC0-t
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve
Measure:Alpha-fetoprotein
Time Frame:baseline, every 6 weeks up to 6 months
Safety Issue:
Description:Change from baseline
Measure:Soluble c-MET
Time Frame:baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment
Safety Issue:
Description:Change from baseline
Measure:Soluble Hepatocyte Growth Factor
Time Frame:baseline, Cycle 1 Days 1, 2 and 15, then Day 1 of each cycle until end of treatment
Safety Issue:
Description:Change from baseline
Measure:Plasma pharmacokinetic parameter: CL/F
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles
Measure:Plasma pharmacokinetic parameter: Cmax
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration
Measure:Plasma pharmacokinetic parameter: Tmax
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration
Measure:Plasma pharmacokinetic parameter: T1/2
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles
Measure:Plasma pharmacokinetic parameter: Racc
Time Frame:Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3
Safety Issue:
Description:Plasma concentration of INC280 versus time profiles

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation

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