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NCT01755767: METIV-HCC

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

Completed Phase 3 Results posted Last updated 6 April 2021
What this trial tests

Phase 3 trial testing Tivantinib in Hepatocellular Carcinoma in 383 participants. Completed in 31 July 2017.

Timeline
27 December 2012
Primary endpoint
28 March 2017
31 July 2017

Quick facts

Lead sponsorDaiichi Sankyo
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment383
Start date27 December 2012
Primary completion28 March 2017
Estimated completion31 July 2017
Sites112 locations across France, Italy, Netherlands, New Zealand, Belgium, Austria, Sweden, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo — full company profile →

Who can join

18 and older, any sex, with Hepatocellular Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · within 36 months

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.

GroupValue95% CI
Tivantinib 120 mg BID Cohort8.46.8 – 10.0
Placebo Matching 120 mg BID Cohort9.17.3 – 10.4
Overall Survival (OS) Rate At Different Time Points 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 Primary · within 36 months

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.

Overall survival at 3 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort86.681.4 – 90.5
Placebo Matching 120 mg BID Cohort85.978.0 – 91.1
Overall survival at 6 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort61.254.5 – 67.2
Placebo Matching 120 mg BID Cohort70.861.5 – 78.3
Overall survival at 9 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort46.940.2 – 53.3
Placebo Matching 120 mg BID Cohort50.540.9 – 59.2
Overall survival at 12 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort36.630.3 – 42.9
Placebo Matching 120 mg BID Cohort38.029.1 – 46.9
Overall survival at 18 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort25.119.4 – 31.2
Placebo Matching 120 mg BID Cohort21.914.3 – 30.5
Overall survival at 24 months
GroupValue95% CI
Tivantinib 120 mg BID Cohort16.211.0 – 22.3
Placebo Matching 120 mg BID Cohort12.25.9 – 20.8
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) Secondary · within 10 months

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.

GroupValue95% CI
Tivantinib 120 mg BID Cohort2.11.9 – 3.0
Placebo Matching 120 mg BID Cohort2.01.9 – 3.6
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 Secondary · Baseline to 30 days after last dose, up to approximately 4 years

Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.

Any TEAEs
GroupValue95% CI
Tivantinib 120 mg BID Cohort214
Placebo Matching 120 mg BID Cohort108
Gastrointestinal Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort159
Placebo Matching 120 mg BID Cohort84
General Disorders & Administration Site Conditions
GroupValue95% CI
Tivantinib 120 mg BID Cohort146
Placebo Matching 120 mg BID Cohort75
Musculoskeletal and Connective Tissue Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort75
Placebo Matching 120 mg BID Cohort34
Respiratory, Thoracic, and Mediastinal Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort70
Placebo Matching 120 mg BID Cohort32
Metabolism and Nutrition Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort65
Placebo Matching 120 mg BID Cohort30
Blood and Lymphatic System Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort64
Placebo Matching 120 mg BID Cohort27
Nervous System Disorders
GroupValue95% CI
Tivantinib 120 mg BID Cohort60
Placebo Matching 120 mg BID Cohort27
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 Secondary · Baseline to 30 days after last dose, up to approximately 4 years

Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.

Any TEAEs
GroupValue95% CI
Tivantinib 240 mg BID Cohort28
Placebo Matching 240 mg BID Cohort14
Blood and Lymphatic System Disorders
GroupValue95% CI
Tivantinib 240 mg BID Cohort20
Placebo Matching 240 mg BID Cohort4
Gastrointestinal Disorders
GroupValue95% CI
Tivantinib 240 mg BID Cohort20
Placebo Matching 240 mg BID Cohort12
General Disorders & Administration Site Conditions
GroupValue95% CI
Tivantinib 240 mg BID Cohort19
Placebo Matching 240 mg BID Cohort9
Investigations
GroupValue95% CI
Tivantinib 240 mg BID Cohort11
Placebo Matching 240 mg BID Cohort8
Respiratory, Thoracic, and Mediastinal Disorders
GroupValue95% CI
Tivantinib 240 mg BID Cohort8
Placebo Matching 240 mg BID Cohort4
Infections and Infestations
GroupValue95% CI
Tivantinib 240 mg BID Cohort7
Placebo Matching 240 mg BID Cohort3
Skin and Subcutaneous Tissue Disorders
GroupValue95% CI
Tivantinib 240 mg BID Cohort7
Placebo Matching 240 mg BID Cohort3

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected from baseline to 30 days after the last dose up to approximately 4 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tivantinib 240 mg BID Cohort
Serious: 17/28 (61%)
Deaths: 28/28
Placebo Matching 240 mg BID Cohort
Serious: 10/15 (67%)
Deaths: 14/15
Tivantinib 120 mg BID Cohort
Serious: 103/225 (46%)
Deaths: 180/225
Placebo Matching 120 mg BID Cohort
Serious: 51/114 (45%)
Deaths: 94/114

Serious adverse events (147 terms)

ReactionSystemTivantinib 240 mg BID CohortPlacebo Matching 240 mg BI…Tivantinib 120 mg BID CohortPlacebo Matching 120 mg BI…
General physical health deteriorationGeneral disorders
Gastrointestinal haemorrhageGastrointestinal disorders
AscitesGastrointestinal disorders
Oesophageal varices haemorrhageGastrointestinal disorders
SepsisInfections and infestations
Liver function test abnormalInvestigations
AnaemiaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Renal failure acuteRenal and urinary disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Hepatic enzyme increasedInvestigations
Respiratory failureRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
Myocardial infarctionCardiac disorders
DiarrhoeaGastrointestinal disorders
Gastric haemorrhageGastrointestinal disorders
Peritoneal haemorrhageGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
Disease progressionGeneral disorders
FatigueGeneral disorders
Other adverse events (89 terms — click to expand)

ReactionSystemTivantinib 240 mg BID CohortPlacebo Matching 240 mg BI…Tivantinib 120 mg BID CohortPlacebo Matching 120 mg BI…
FatigueGeneral disorders
Oedema peripheralGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
Abdominal painGastrointestinal disorders
AscitesGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
BradycardiaCardiac disorders
ConstipationGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Abdominal pain upperGastrointestinal disorders
VomitingGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
HypertensionVascular disorders
DizzinessNervous system disorders
General physical health deteriorationGeneral disorders
Aspartate aminotransferase increasedInvestigations
HeadacheNervous system disorders
Sinus bradycardiaCardiac disorders
DyspepsiaGastrointestinal disorders
Blood bilirubin increasedInvestigations
Abdominal distensionGastrointestinal disorders
Weight decreasedInvestigations
Muscle spasmsMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
NasopharyngitisInfections and infestations
RashSkin and subcutaneous tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
Musculoskeletal painMusculoskeletal and connective tissue disorders
FallInjury, poisoning and procedural complications
HyponatraemiaMetabolism and nutrition disorders
StomatitisGastrointestinal disorders

Most-reported serious reactions: General physical health deterioration, Gastrointestinal haemorrhage, Ascites, Oesophageal varices haemorrhage, Sepsis, Liver function test abnormal, Anaemia, Abdominal pain.

Data from ClinicalTrials.gov NCT01755767 adverse events section.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis.
    Sia D, Villanueva A, Friedman SL, Llovet JM. · · 2017 · cited 864× · PMID 28043904 · DOI 10.1053/j.gastro.2016.11.048
  2. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities.
    Zhang Y, Xia M, Jin K, Wang S, et al · · 2018 · cited 410× · PMID 29455668 · DOI 10.1186/s12943-018-0796-y
  3. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
    Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
  4. Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study.
    Rimassa L, Assenat E, Peck-Radosavljevic M, Pracht M, et al · · 2018 · cited 273× · PMID 29625879 · DOI 10.1016/s1470-2045(18)30146-3
  5. MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma.
    Moon H, Ro SW. · · 2021 · cited 217× · PMID 34204242 · DOI 10.3390/cancers13123026
  6. Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma.
    Bouattour M, Raymond E, Qin S, Cheng AL, et al · · 2018 · cited 199× · PMID 28862760 · DOI 10.1002/hep.29496
  7. Recent advances in hepatocellular carcinoma therapy.
    Dutta R, Mahato RI. · · 2017 · cited 198× · PMID 28174094 · DOI 10.1016/j.pharmthera.2017.02.010
  8. Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies.
    Alqahtani A, Khan Z, Alloghbi A, Said Ahmed TS, et al · · 2019 · cited 170× · PMID 31450841 · DOI 10.3390/medicina55090526

Verify or expand the search:

Other trials of Tivantinib

Trials testing the same drug.

Other recruiting trials for Hepatocellular Carcinoma

Currently open trials in the same condition.

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Trials by the same sponsor.

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