Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy (METIV-HCC)
12 marzo 2021 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
383
Fase
- Fase 3
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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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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Graz, Austria
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Innsbruck, Austria
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Linz, Austria
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Wien, Austria
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Brussels, Belgio
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Ghent, Belgio
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Leuven, Belgio
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Liege, Belgio
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Barretos, Brasile
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Rio de Janeiro, Brasile
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RS
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Porto Alegre, RS, Brasile
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SP
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Sao Paulo, SP, Brasile
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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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Amiens Cedex 1, Francia
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Bordeaux Cedex, Francia
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Caen Cedex 09, Francia
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Clichy, Francia
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Creteil, Francia
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Grenoble, Francia
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Lille Cedex, Francia
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Marseille Cedex 09, Francia
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Montpellier, Francia
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Paris Cedex, Francia
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Paris Cedex 12, Francia
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Reims Cedex, Francia
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Rennes Cedex, Francia
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Toulouse Cedex 09, Francia
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Villejuif Cedex, Francia
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Aachen, Germania
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Berlin, Germania
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Bonn, Germania
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Duesseldorf, Germania
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Essen, Germania
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Frankfurt am Main, Germania
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Hamburg, Germania
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Hannover, Germania
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Heidelberg, Germania
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Leipzig, Germania
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Magdeburg, Germania
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Mainz, Germania
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Muenchen, Germania
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Munich, Germania
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Regensburg, Germania
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Tuebingen, Germania
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Ulm, Germania
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Wuerzburg, Germania
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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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Auckland, Nuova Zelanda
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Amsterdam, Olanda
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Lisboa, Portogallo
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Porto, Portogallo
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Vila Real, Portogallo
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Alicante, Spagna
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Barcelona, Spagna
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Cordoba, Spagna
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Madrid, Spagna
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Sabadell, Spagna
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Santander, Spagna
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Valencia, Spagna
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Zaragoza, Spagna
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A Coruña
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Santiago de Compostela, A Coruña, Spagna
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Asturias
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Oviedo, Asturias, Spagna
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Madrid
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Majadahonda, Madrid, Spagna
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Navarra
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Pamplona, Navarra, Spagna
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Arizona
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Tucson, Arizona, Stati Uniti
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California
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Los Angeles, California, Stati Uniti
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Orange, California, Stati Uniti
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District of Columbia
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Washington, District of Columbia, Stati Uniti
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Florida
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Gainesville, Florida, Stati Uniti
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Illinois
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Chicago, Illinois, Stati Uniti
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Kansas
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Westwood, Kansas, Stati Uniti
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Louisiana
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New Orleans, Louisiana, Stati Uniti
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Maine
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Scarborough, Maine, Stati Uniti
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Massachusetts
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Boston, Massachusetts, Stati Uniti
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Michigan
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Detroit, Michigan, Stati Uniti
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Minnesota
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Minneapolis, Minnesota, Stati Uniti
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New Jersey
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Hackensack, New Jersey, Stati Uniti
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New York
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New York, New York, Stati Uniti
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Pennsylvania
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Philadelphia, Pennsylvania, Stati Uniti
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South Carolina
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Charleston, South Carolina, Stati Uniti
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Texas
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Dallas, Texas, Stati Uniti
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Galveston, Texas, Stati Uniti
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Houston, Texas, Stati Uniti
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Washington
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Seattle, Washington, Stati Uniti
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Gothenburg, Svezia
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Stockholm, Svezia
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Bern, Svizzera
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Zurich, Svizzera
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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
Altri nomi:
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Sperimentale: 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
Altri nomi:
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Comparatore placebo: 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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Compresse placebo corrispondenti
Altri nomi:
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Comparatore placebo: 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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Compresse placebo corrispondenti
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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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
Lasso di tempo: 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
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
27 dicembre 2012
Completamento primario (Effettivo)
28 marzo 2017
Completamento dello studio (Effettivo)
31 luglio 2017
Date di iscrizione allo studio
Primo inviato
19 dicembre 2012
Primo inviato che soddisfa i criteri di controllo qualità
19 dicembre 2012
Primo Inserito (Stima)
24 dicembre 2012
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
6 aprile 2021
Ultimo aggiornamento inviato che soddisfa i criteri QC
12 marzo 2021
Ultimo verificato
1 marzo 2021
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- ARQ197-A-U303
- 2012-003308-10 (Numero EudraCT)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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Yonsei UniversityNon ancora reclutamento