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

Title

  • Brief Title: Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) 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

  • ORG STUDY ID: ARQ197-A-U303
  • SECONDARY ID: 2012-003308-10
  • NCT ID: NCT01755767

Conditions

  • Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
TivantinibARQ197Tivantinib 120 mg BID Cohort
PlaceboPlacebo comparatorPlacebo Matching 120 mg BID Cohort

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

NameTypeDescriptionInterventions
Tivantinib 240 mg BID CohortExperimentalThe tivantinib dosage of 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg.
  • Tivantinib
Tivantinib 120 mg BID CohortExperimentalTivantinib 120 mg is administered by oral tablet BID, once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).
  • Tivantinib
Placebo Matching 240 mg BID CohortPlacebo ComparatorMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
  • Placebo
Placebo Matching 120 mg BID CohortPlacebo ComparatorMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
  • 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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Time Frame:within 36 months
Safety Issue:
Description:Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.

Secondary Outcome Measures

Measure:Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population)
Time Frame:within 10 months
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause. The rate of PFS (percentage of participants still alive without disease progression) was determined only in the tivantinib 120 mg BID cohort.
Measure:Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Time Frame:Baseline to 30 days after last dose, up to approximately 4 years
Safety Issue:
Description:Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.
Measure:Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Time Frame:Baseline to 30 days after last dose, up to approximately 4 years
Safety Issue:
Description:Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • MET diagnostic-high
  • Unresectable
  • Hepatocellular
  • Carcinoma
  • c-Met inhibitor

Last Updated

April 6, 2021