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

12. marts 2021 opdateret af: Daiichi Sankyo, Inc.

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

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

383

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Argentina
      • Pilar, Argentina
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
    • Caba
      • Buenos Aires, Caba, Argentina
  • Australien
    • New South Wales
      • Camperdown, New South Wales, Australien
    • Victoria
      • Heidelberg, Victoria, Australien
      • Melbourne, Victoria, Australien
    • Western Australia
      • Nedlands, Western Australia, Australien
  • Belgien
      • Brussels, Belgien
      • Ghent, Belgien
      • Leuven, Belgien
      • Liege, Belgien
  • Brasilien
      • Barretos, Brasilien
      • Rio de Janeiro, Brasilien
    • RS
      • Porto Alegre, RS, Brasilien
    • SP
      • Sao Paulo, SP, Brasilien
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Ontario
      • Toronto, Ontario, Canada
  • Forenede Stater
    • Arizona
      • Tucson, Arizona, Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater
      • Orange, California, Forenede Stater
    • District of Columbia
      • Washington, District of Columbia, Forenede Stater
    • Florida
      • Gainesville, Florida, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Kansas
      • Westwood, Kansas, Forenede Stater
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater
    • Maine
      • Scarborough, Maine, Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater
    • Michigan
      • Detroit, Michigan, Forenede Stater
    • Minnesota
      • Minneapolis, Minnesota, Forenede Stater
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater
    • New York
      • New York, New York, Forenede Stater
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater
    • South Carolina
      • Charleston, South Carolina, Forenede Stater
    • Texas
      • Dallas, Texas, Forenede Stater
      • Galveston, Texas, Forenede Stater
      • Houston, Texas, Forenede Stater
    • Washington
      • Seattle, Washington, Forenede Stater
  • Frankrig
      • Amiens Cedex 1, Frankrig
      • Bordeaux Cedex, Frankrig
      • Caen Cedex 09, Frankrig
      • Clichy, Frankrig
      • Creteil, Frankrig
      • Grenoble, Frankrig
      • Lille Cedex, Frankrig
      • Marseille Cedex 09, Frankrig
      • Montpellier, Frankrig
      • Paris Cedex, Frankrig
      • Paris Cedex 12, Frankrig
      • Reims Cedex, Frankrig
      • Rennes Cedex, Frankrig
      • Toulouse Cedex 09, Frankrig
      • Villejuif Cedex, Frankrig
  • Holland
      • Amsterdam, Holland
  • Italien
      • Benevento, Italien, 82100
      • Bergamo, Italien
      • Bologna, Italien
      • Catania, Italien
      • Firenze, Italien
      • Milano, Italien
      • Modena, Italien
      • Napoli, Italien
      • Padova, Italien
      • Parma, Italien
      • Pavia, Italien
      • Pisa, Italien
      • Reggio Emilia, Italien
      • Roma, Italien
      • Turin, Italien
    • Forli-Cesena
      • Meldola, Forli-Cesena, Italien
    • Milano
      • Rozzano, Milano, Italien
    • Torino
      • Orbassano (TO), Torino, Italien
  • New Zealand
      • Auckland, New Zealand
  • Portugal
      • Lisboa, Portugal
      • Porto, Portugal
      • Vila Real, Portugal
  • Schweiz
      • Bern, Schweiz
      • Zurich, Schweiz
  • Spanien
      • Alicante, Spanien
      • Barcelona, Spanien
      • Cordoba, Spanien
      • Madrid, Spanien
      • Sabadell, Spanien
      • Santander, Spanien
      • Valencia, Spanien
      • Zaragoza, Spanien
    • A Coruña
      • Santiago de Compostela, A Coruña, Spanien
    • Asturias
      • Oviedo, Asturias, Spanien
    • Madrid
      • Majadahonda, Madrid, Spanien
    • Navarra
      • Pamplona, Navarra, Spanien
  • Sverige
      • Gothenburg, Sverige
      • Stockholm, Sverige
  • Tyskland
      • Aachen, Tyskland
      • Berlin, Tyskland
      • Bonn, Tyskland
      • Duesseldorf, Tyskland
      • Essen, Tyskland
      • Frankfurt am Main, Tyskland
      • Hamburg, Tyskland
      • Hannover, Tyskland
      • Heidelberg, Tyskland
      • Leipzig, Tyskland
      • Magdeburg, Tyskland
      • Mainz, Tyskland
      • Muenchen, Tyskland
      • Munich, Tyskland
      • Regensburg, Tyskland
      • Tuebingen, Tyskland
      • Ulm, Tyskland
      • Wuerzburg, Tyskland
  • Østrig
      • Graz, Østrig
      • Innsbruck, Østrig
      • Linz, Østrig
      • Wien, Østrig

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Tivantinib 240 mg BID Cohort
The 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.
Medicin: Tivantinib
Tivantinib tablets
Andre navne:
  • ARQ197
Eksperimentel: Tivantinib 120 mg BID Cohort
Tivantinib 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).
Medicin: Tivantinib
Tivantinib tablets
Andre navne:
  • ARQ197
Placebo komparator: Placebo Matching 240 mg BID Cohort
Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Medicin: Placebo
Matchende placebotabletter
Andre navne:
  • Placebo komparator
Placebo komparator: Placebo Matching 120 mg BID Cohort
Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Medicin: Placebo
Matchende placebotabletter
Andre navne:
  • Placebo komparator

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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
Tidsramme: 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.
within 36 months
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
Tidsramme: 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.
within 36 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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)
Tidsramme: 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.
within 10 months
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
Tidsramme: 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.
Baseline to 30 days after last dose, up to approximately 4 years
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
Tidsramme: 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.
Baseline to 30 days after last dose, up to approximately 4 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Daiichi Sankyo, Inc.

Samarbejdspartnere

ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

27. december 2012

Primær færdiggørelse (Faktiske)

28. marts 2017

Studieafslutning (Faktiske)

31. juli 2017

Datoer for studieregistrering

Først indsendt

19. december 2012

Først indsendt, der opfyldte QC-kriterier

19. december 2012

Først opslået (Skøn)

24. december 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. april 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. marts 2021

Sidst verificeret

1. marts 2021

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • ARQ197-A-U303
  • 2012-003308-10 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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