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.
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
| Drug | Synonyms | Arms |
|---|
| INC280 | | INC280 |
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
| Name | Type | Description | Interventions |
|---|
| INC280 | Experimental | 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. | |
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: | Active, not recruiting |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation
Last Updated
February 24, 2021
