Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy (METIV-HCC)
12. mars 2021 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert 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.
Studietype
Intervensjonell
Registrering (Faktiske)
383
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Pilar, Argentina
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Buenos Aires
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
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Caba
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Buenos Aires, Caba, Argentina
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New South Wales
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Camperdown, New South Wales, Australia
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Victoria
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Heidelberg, Victoria, Australia
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Melbourne, Victoria, Australia
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Western Australia
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Nedlands, Western Australia, Australia
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Brussels, Belgia
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Ghent, Belgia
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Leuven, Belgia
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Liege, Belgia
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Barretos, Brasil
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Rio de Janeiro, Brasil
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RS
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Porto Alegre, RS, Brasil
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SP
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Sao Paulo, SP, Brasil
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British Columbia
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Vancouver, British Columbia, Canada
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Ontario
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Toronto, Ontario, Canada
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Arizona
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Tucson, Arizona, Forente stater
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California
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Los Angeles, California, Forente stater
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Orange, California, Forente stater
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District of Columbia
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Washington, District of Columbia, Forente stater
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Florida
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Gainesville, Florida, Forente stater
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Illinois
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Chicago, Illinois, Forente stater
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Kansas
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Westwood, Kansas, Forente stater
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Louisiana
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New Orleans, Louisiana, Forente stater
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Maine
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Scarborough, Maine, Forente stater
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Massachusetts
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Boston, Massachusetts, Forente stater
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Michigan
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Detroit, Michigan, Forente stater
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Minnesota
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Minneapolis, Minnesota, Forente stater
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New Jersey
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Hackensack, New Jersey, Forente stater
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New York
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New York, New York, Forente stater
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Pennsylvania
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Philadelphia, Pennsylvania, Forente stater
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South Carolina
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Charleston, South Carolina, Forente stater
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Texas
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Dallas, Texas, Forente stater
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Galveston, Texas, Forente stater
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Houston, Texas, Forente stater
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Washington
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Seattle, Washington, Forente stater
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Amiens Cedex 1, Frankrike
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Bordeaux Cedex, Frankrike
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Caen Cedex 09, Frankrike
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Clichy, Frankrike
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Creteil, Frankrike
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Grenoble, Frankrike
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Lille Cedex, Frankrike
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Marseille Cedex 09, Frankrike
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Montpellier, Frankrike
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Paris Cedex, Frankrike
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Paris Cedex 12, Frankrike
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Reims Cedex, Frankrike
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Rennes Cedex, Frankrike
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Toulouse Cedex 09, Frankrike
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Villejuif Cedex, Frankrike
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Benevento, Italia, 82100
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Bergamo, Italia
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Bologna, Italia
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Catania, Italia
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Firenze, Italia
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Milano, Italia
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Modena, Italia
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Napoli, Italia
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Padova, Italia
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Parma, Italia
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Pavia, Italia
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Pisa, Italia
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Reggio Emilia, Italia
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Roma, Italia
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Turin, Italia
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Forli-Cesena
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Meldola, Forli-Cesena, Italia
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Milano
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Rozzano, Milano, Italia
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Torino
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Orbassano (TO), Torino, Italia
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Amsterdam, Nederland
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Auckland, New Zealand
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Lisboa, Portugal
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Porto, Portugal
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Vila Real, Portugal
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Alicante, Spania
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Barcelona, Spania
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Cordoba, Spania
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Madrid, Spania
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Sabadell, Spania
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Santander, Spania
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Valencia, Spania
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Zaragoza, Spania
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A Coruña
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Santiago de Compostela, A Coruña, Spania
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Asturias
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Oviedo, Asturias, Spania
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Madrid
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Majadahonda, Madrid, Spania
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Navarra
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Pamplona, Navarra, Spania
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Bern, Sveits
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Zurich, Sveits
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Gothenburg, Sverige
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Stockholm, Sverige
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Aachen, Tyskland
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Berlin, Tyskland
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Bonn, Tyskland
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Duesseldorf, Tyskland
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Essen, Tyskland
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Frankfurt am Main, Tyskland
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Hamburg, Tyskland
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Hannover, Tyskland
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Heidelberg, Tyskland
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Leipzig, Tyskland
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Magdeburg, Tyskland
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Mainz, Tyskland
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Muenchen, Tyskland
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Munich, Tyskland
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Regensburg, Tyskland
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Tuebingen, Tyskland
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Ulm, Tyskland
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Wuerzburg, Tyskland
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Graz, Østerrike
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Innsbruck, Østerrike
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Linz, Østerrike
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Wien, Østerrike
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: 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.
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Tivantinib tablets
Andre navn:
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Eksperimentell: 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).
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Tivantinib tablets
Andre navn:
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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.
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Matchende placebotabletter
Andre navn:
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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.
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Matchende placebotabletter
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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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
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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.
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within 36 months
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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
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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.
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within 36 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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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
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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.
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within 10 months
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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
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Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.
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Baseline to 30 days after last dose, up to approximately 4 years
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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
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Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.
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Baseline to 30 days after last dose, up to approximately 4 years
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
27. desember 2012
Primær fullføring (Faktiske)
28. mars 2017
Studiet fullført (Faktiske)
31. juli 2017
Datoer for studieregistrering
Først innsendt
19. desember 2012
Først innsendt som oppfylte QC-kriteriene
19. desember 2012
Først lagt ut (Anslag)
24. desember 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
6. april 2021
Siste oppdatering sendt inn som oppfylte QC-kriteriene
12. mars 2021
Sist bekreftet
1. mars 2021
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- ARQ197-A-U303
- 2012-003308-10 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .