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
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Novartis Pharmaceuticals
- Locations
- 3
- Primary Endpoint
- Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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.
- •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.
Arms & Interventions
INC280 plus best supportive care
Approximately 46 patients will be treated with INC280 600 mg twice a day plus best supportive care.
Intervention: INC280 (Drug)
Placebo plus best supportive care
Approximately 23 patients will be treated with matching placebo twice a day plus best supportive care.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Time Frame: 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 Outcomes
- Overall Response Rate(baseline, every 6 weeks up to 6 months)
- Safety: hematology and chemistry values, vital signs, electrocardiograms(From baseline until end of treatment, average 6 months from baseline)
- Disease Control Rate(baseline, every 6 weeks up to 6 months)
- Safety: adverse events, serious adverse events(From baseline until 30 days post study treatment)
- Best Overall Response(date of treatment, every 6 weeks up to 6 months)
- Overall Survival(randomization until death, average 10 months)
- Tolerability of study drug(From date of randomization until end of treatment, average 6 months from baseline)
- Progression Free Survival(randomization, every 6 weeks up to 6 months)