Clinical Trials /

Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy

NCT01755767

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Completed

Phase:

Phase 3

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Tivantinib</span> in Subjects With Inoperable Hepatocellular Carcinoma Who Have Been Treated With One Prior Therapy

Title

  • Brief Title: Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma Who Have Been Treated With One Prior Therapy
  • Official Title: A Phase 3, Randomized, Double-Blind Study of Tivantinib (ARQ 197) in Subjects With MET Diagnostic-High Inoperable Hepatocellular Carcinoma Treated With One Prior Systemic Therapy
  • Clinical Trial IDs

    NCT ID: NCT01755767

    ORG ID: ARQ197-A-U303

    Trial Conditions

    Hepatocellular Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Tivantinib ARQ197 Tivantinib
    Placebo Placebo

    Trial Purpose

    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.

    Detailed Description

    Expression of c-Met in tumors correlates with aggressive hepatocellular carcinoma (HCC)
    features. Overexpression of the receptor in tumor samples or high level of blood HGF in
    subjects is related to higher recurrence rate after surgery for HCC, while high c-Met
    expression correlates with shorter survival in HCC subjects. In summary, c-Met holds an
    important prognostic role in the natural history of HCC. This Phase 3 study in MET
    Diagnostic-High inoperable HCC subjects has been designed based on the results from the
    randomized, controlled Phase 2 study conducted by ArQule, Inc. with tivantinib versus
    placebo in subjects with MET Diagnostic-High inoperable HCC who have failed one prior
    systemic therapy, mentioned above. The purpose of this study is to confirm the efficacy of
    tivantinib in MET Diagnostic-High HCC subjects who were previously treated with one systemic
    therapy, and to further evaluate the safety profile of the experimental drug in this subject
    population.

    Trial Arms

    Name Type Description Interventions
    Tivantinib Experimental Tivantinib
    Placebo Placebo Comparator Placebo

    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

    - ECOG Performance Status (PS) of <= equal to 1

    - 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. Tumor lesions previously treated
    with local therapy should demonstrate clear dimensional increase by radiographic
    assessment in order to be selected as target lesion(s) at baseline.

    - Adequate bone marrow, liver, and renal functions at Screening Visit, defined as:

    platelet count greater than or equal to 60 x 10^9/L; hemoglobin greater than or equal to
    9.0 g/dL; absolute neutrophil count (ANC) <= 1.5 x 10^9/L; total bilirubin <= 2 mg/dL;
    Alanine transaminase (ALT) and aspartate aminotransferase (AST) <= 5 x upper limit of
    normal (ULN); serum creatinine <= 1.5 x ULN; albumin <= 2.8 g/dL; international normalized
    ratio (INR) 0.8 to ULN or <= 3 for subjects receiving anticoagulant such as coumadin or
    heparin. Subjects who are therapeutically anticoagulated are allowed to participate
    provided that prior to anticoagulant therapy no evidence of underlying defect in
    coagulation exists

    - Women of childbearing potential must have a negative serum pregnancy test performed
    within 14 days prior to the randomization (where demanded by local regulations, test
    may be required within 72 hours prior to randomization)

    - Male and female subjects of child-bearing potential must agree to use double-barrier
    contraceptive measures, oral contraception, or avoidance of intercourse during the
    study and for 90 days after last investigational drug dose received

    - Life expectancy of at least 12 weeks

    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 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall survival (OS) in Intent to Treat (ITT) population

    Secondary Outcome Measures

    Progression free survival (PFS)

    Safety

    Trial Keywords

    MET diagnostic-high

    Unresectable

    Hepatocellular

    Carcinoma

    c-Met inhibitor