A Randomized Double-blind, Placebo-controlled Japanese Phase III Trial of ARQ 197 in Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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The present clinical trial is aiming to evaluate efficacy of ARQ 197 in patients with hepatocellular carcinoma (HCC), who were resistant or intolerable to one systemic chemotherapy regimen including sorafenib.

Official Title
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A Phase III Randomized Double-blind, Placebo-controlled Trial of ARQ 197 in Subjects With c-MET Diagnostic-high Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Sorafenib Therapy

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: ARQ197
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent form ≥20 years old Inoperable HCC which is not eligible for locoregional therapy Diagnosed as c-Met high in tumor sample Radiographic progression is confirmed during or after systemic chemotherapy including sorafenib, or those who are intolerance to the chemotherapy. Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or 1 Child-Pugh Class A Having measurable target lesions which are defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Negative pregnancy test results Adequate organ function Life expectancy of at least 12 weeks Exclusion Criteria: More than 2 prior systemic chemotherapy. Prior therapy of c-Met inhibitor (including antibody) Any systemic therapy within ≤2 weeks prior to the randomization Locoregional therapy within ≤4 weeks prior to randomization. Major surgery within ≤4 weeks prior to the randomization Concurrent cancer within ≤5 years prior to the randomization History of cardiac diseases Active clinically serious infections defined as ≥ Grade 3 according to Common Toxicity Criteria for Adverse Effects (CTCAE) 4.0 Any psychological disorder affecting Informed Consent Diagnosis positive for anti-HIV antibody and/or anti-HTLV-1 antibody Blood or albumin transfusion within ≤14 days prior to the screening test Concurrent interferon therapy against Hepatitis B Virus (HBV)/ Hepatitis C Virus (HCV) Symptomatic brain metastases History of liver transplantation Inability to swallow oral medications Confirmed interstitial lung disease Pleural effusion and/or clinically significant ascites Pregnancy or breast-feeding Without consent to effective single or combined contraceptive methods

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ 197<br>Daily oral dose | Drug: ARQ197<br> <br> |
| Placebo Comparator: Placebo<br>Daily oral dose | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Progression-free survival will be compared between ARQ 197 group and Placebo group, to prove the efficacy of ARQ 197 in the population. | Estimated median of 8-12 weeks in PFS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The date of the events was followed every three months after the end of the treatments of the study drug. | Estimated median of 24 weeks in overall survival |