Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Tivantinib; Placebo
Intervention description: Tivantinib tablets; Matching placebo tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 383.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MET diagnostic-high; Unresectable; Hepatocellular; Carcinoma; c-Met inhibitor

Summary:

      The purpose of this study is to determine if tivantinib (ARQ 197) is effective in treating
      patients with MET diagnostic-high hepatocellular carcinoma (liver cancer) who have already
      been treated once with another therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed HCC that is inoperable (where surgery is not indicated due to
             disease extension, co-morbidities, or other technical reasons), and not eligible for
             local therapy

          -  MET Diagnostic-High tissue reported by the central authorized laboratory using
             archival or recent biopsy tumor samples

          -  Received at least 4 weeks of one prior sorafenib containing systemic therapy and then
             experienced documented radiographic disease progression; or inability to tolerate
             prior therapy received for at least a minimum period of time.

          -  Discontinued prior systemic treatment or any investigational drug for at least 2 weeks
             (14 days) or for at least 3 weeks for IV anti-cancer drugs, prior to the study
             randomization

          -  Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial
             embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol
             injection, or cryoablation) must have been completed >= 4 weeks prior to randomization

          -  Measurable disease as defined by the RECIST v1.1.

        Exclusion Criteria:

          -  More than 1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed;
             experimental systemic therapy for inoperable HCC given before or after sorafenib
             counts as separate regimen and is not allowed)

          -  Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results

          -  Previous or concurrent cancer that is distinct from HCC in primary site or histology,
             EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial
             bladder tumors. Any cancer curatively treated more than 3 years prior to enrollment is
             permitted.

          -  History of congestive heart failure defined as Class II to IV per New York Heart
             Association (NYHA) classification within 6 months prior to study entry; active
             coronary artery disease (CAD); clinically significant bradycardia or other
             uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade 3 according
             to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
             (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within 6 months
             prior to study entry (myocardial infarction occurring more than 6 months prior to
             study entry is permitted)

          -  Active clinically serious infections defined as >= Grade 3 according to NCI CTCAE

          -  Any medical, psychological, or social conditions, particularly if unstable, including
             substance abuse, that may, in the opinion of the Investigator, interfere with the
             subject's safety or participation in the study, protocol compliance, or evaluation of
             the study results

          -  Known human immunodeficiency virus (HIV) infection

          -  Blood or albumin transfusion within 5 days prior to the blood draw being used to
             confirm eligibility

          -  Concomitant interferon therapy or therapies for active Hepatitis C virus (HCV)
             infection

          -  Pregnancy or breast-feeding

          -  History of liver transplant

          -  Inability to swallow oral medications

          -  Clinically significant gastrointestinal bleeding occurring <= 4 weeks prior to
             randomization

          -  Pleural effusion or clinically evident (visible or palpable) ascites