Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy (METIV-HCC)
12 mars 2021 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
383
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Aachen, Allemagne
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Berlin, Allemagne
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Bonn, Allemagne
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Duesseldorf, Allemagne
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Essen, Allemagne
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Frankfurt am Main, Allemagne
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Hamburg, Allemagne
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Hannover, Allemagne
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Heidelberg, Allemagne
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Leipzig, Allemagne
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Magdeburg, Allemagne
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Mainz, Allemagne
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Muenchen, Allemagne
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Munich, Allemagne
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Regensburg, Allemagne
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Tuebingen, Allemagne
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Ulm, Allemagne
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Wuerzburg, Allemagne
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Pilar, Argentine
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Buenos Aires
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentine
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Caba
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Buenos Aires, Caba, Argentine
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New South Wales
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Camperdown, New South Wales, Australie
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Victoria
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Heidelberg, Victoria, Australie
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Melbourne, Victoria, Australie
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Western Australia
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Nedlands, Western Australia, Australie
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Brussels, Belgique
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Ghent, Belgique
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Leuven, Belgique
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Liege, Belgique
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Barretos, Brésil
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Rio de Janeiro, Brésil
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RS
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Porto Alegre, RS, Brésil
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SP
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Sao Paulo, SP, Brésil
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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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Alicante, Espagne
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Barcelona, Espagne
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Cordoba, Espagne
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Madrid, Espagne
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Sabadell, Espagne
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Santander, Espagne
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Valencia, Espagne
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Zaragoza, Espagne
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A Coruña
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Santiago de Compostela, A Coruña, Espagne
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Asturias
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Oviedo, Asturias, Espagne
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Madrid
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Majadahonda, Madrid, Espagne
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Navarra
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Pamplona, Navarra, Espagne
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Amiens Cedex 1, France
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Bordeaux Cedex, France
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Caen Cedex 09, France
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Clichy, France
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Creteil, France
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Grenoble, France
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Lille Cedex, France
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Marseille Cedex 09, France
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Montpellier, France
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Paris Cedex, France
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Paris Cedex 12, France
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Reims Cedex, France
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Rennes Cedex, France
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Toulouse Cedex 09, France
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Villejuif Cedex, France
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Benevento, Italie, 82100
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Bergamo, Italie
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Bologna, Italie
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Catania, Italie
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Firenze, Italie
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Milano, Italie
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Modena, Italie
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Napoli, Italie
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Padova, Italie
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Parma, Italie
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Pavia, Italie
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Pisa, Italie
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Reggio Emilia, Italie
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Roma, Italie
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Turin, Italie
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Forli-Cesena
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Meldola, Forli-Cesena, Italie
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Milano
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Rozzano, Milano, Italie
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Torino
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Orbassano (TO), Torino, Italie
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Graz, L'Autriche
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Innsbruck, L'Autriche
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Linz, L'Autriche
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Wien, L'Autriche
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Lisboa, Le Portugal
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Porto, Le Portugal
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Vila Real, Le Portugal
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Auckland, Nouvelle-Zélande
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Amsterdam, Pays-Bas
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Bern, Suisse
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Zurich, Suisse
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Gothenburg, Suède
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Stockholm, Suède
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Arizona
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Tucson, Arizona, États-Unis
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California
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Los Angeles, California, États-Unis
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Orange, California, États-Unis
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District of Columbia
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Washington, District of Columbia, États-Unis
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Florida
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Gainesville, Florida, États-Unis
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Illinois
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Chicago, Illinois, États-Unis
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Kansas
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Westwood, Kansas, États-Unis
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Louisiana
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New Orleans, Louisiana, États-Unis
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Maine
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Scarborough, Maine, États-Unis
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Massachusetts
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Boston, Massachusetts, États-Unis
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Michigan
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Detroit, Michigan, États-Unis
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Minnesota
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Minneapolis, Minnesota, États-Unis
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New Jersey
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Hackensack, New Jersey, États-Unis
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New York
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New York, New York, États-Unis
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis
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South Carolina
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Charleston, South Carolina, États-Unis
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Texas
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Dallas, Texas, États-Unis
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Galveston, Texas, États-Unis
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Houston, Texas, États-Unis
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Washington
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Seattle, Washington, États-Unis
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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
Autres noms:
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Expérimental: 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
Autres noms:
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Comparateur 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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Comprimés placebo correspondants
Autres noms:
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Comparateur 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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Comprimés placebo correspondants
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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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
Délai: 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
Délai: 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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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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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)
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
27 décembre 2012
Achèvement primaire (Réel)
28 mars 2017
Achèvement de l'étude (Réel)
31 juillet 2017
Dates d'inscription aux études
Première soumission
19 décembre 2012
Première soumission répondant aux critères de contrôle qualité
19 décembre 2012
Première publication (Estimation)
24 décembre 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
6 avril 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
12 mars 2021
Dernière vérification
1 mars 2021
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- ARQ197-A-U303
- 2012-003308-10 (Numéro EudraCT)
Plan pour les données individuelles des participants (IPD)
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