Advanced Hepatocellular Carcinoma
Conditions
Keywords
INC280, advanced hepatocellular carcinoma, c-MET pathway dysregulation.
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.
Interventions
DRUGINC280
INC280 will be administered orally and continuously on a twice a day dosing schedule.
DRUGPlacebo
Placebo will be administered orally and continuously on a twice a day dosing schedule.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 | baseline, 6 weeks up to 6 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | baseline, every 6 weeks up to 6 months | 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 | baseline, every 6 weeks up to 6 months | 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 | randomization, every 6 weeks up to 6 months | 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. |
| Best Overall Response | date of treatment, every 6 weeks up to 6 months | 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. |
| Safety: adverse events, serious adverse events | From baseline until 30 days post study treatment | Frequency, duration and severity of adverse events. |
| Safety: hematology and chemistry values, vital signs, electrocardiograms | From baseline until end of treatment, average 6 months from baseline | Change from baseline values. |
| Tolerability of study drug | From date of randomization until end of treatment, average 6 months from baseline | Tolerability will be assessed by summarizing the number of dose interruptions, dose reductions and dose intensity. |
| Overall Survival | randomization until death, average 10 months | 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. |
Countries
Australia, France, Germany, Hong Kong, Spain, Switzerland, United States
Outcome results
None listed