Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy (METIV-HCC)
12 de marzo de 2021 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 de estudio
Intervencionista
Inscripción (Actual)
383
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Aachen, Alemania
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Berlin, Alemania
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Bonn, Alemania
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Duesseldorf, Alemania
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Essen, Alemania
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Frankfurt am Main, Alemania
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Hamburg, Alemania
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Hannover, Alemania
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Heidelberg, Alemania
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Leipzig, Alemania
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Magdeburg, Alemania
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Mainz, Alemania
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Muenchen, Alemania
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Munich, Alemania
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Regensburg, Alemania
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Tuebingen, Alemania
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Ulm, Alemania
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Wuerzburg, Alemania
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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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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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Brussels, Bélgica
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Ghent, Bélgica
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Leuven, Bélgica
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Liege, Bélgica
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British Columbia
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Vancouver, British Columbia, Canadá
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Ontario
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Toronto, Ontario, Canadá
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Alicante, España
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Barcelona, España
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Cordoba, España
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Madrid, España
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Sabadell, España
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Santander, España
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Valencia, España
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Zaragoza, España
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A Coruña
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Santiago de Compostela, A Coruña, España
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Asturias
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Oviedo, Asturias, España
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Madrid
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Majadahonda, Madrid, España
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Navarra
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Pamplona, Navarra, España
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Arizona
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Tucson, Arizona, Estados Unidos
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California
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Los Angeles, California, Estados Unidos
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Orange, California, Estados Unidos
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District of Columbia
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Washington, District of Columbia, Estados Unidos
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Florida
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Gainesville, Florida, Estados Unidos
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Illinois
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Chicago, Illinois, Estados Unidos
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Kansas
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Westwood, Kansas, Estados Unidos
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Louisiana
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New Orleans, Louisiana, Estados Unidos
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Maine
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Scarborough, Maine, Estados Unidos
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Massachusetts
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Boston, Massachusetts, Estados Unidos
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Michigan
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Detroit, Michigan, Estados Unidos
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Minnesota
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Minneapolis, Minnesota, Estados Unidos
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New Jersey
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Hackensack, New Jersey, Estados Unidos
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New York
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New York, New York, Estados Unidos
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Pennsylvania
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Philadelphia, Pennsylvania, Estados Unidos
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South Carolina
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Charleston, South Carolina, Estados Unidos
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Texas
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Dallas, Texas, Estados Unidos
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Galveston, Texas, Estados Unidos
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Houston, Texas, Estados Unidos
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Washington
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Seattle, Washington, Estados Unidos
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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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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, Nueva Zelanda
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Amsterdam, Países Bajos
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Lisboa, Portugal
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Porto, Portugal
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Vila Real, Portugal
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Gothenburg, Suecia
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Stockholm, Suecia
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Bern, Suiza
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Zurich, Suiza
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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 de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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
Otros nombres:
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Experimental: 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
Otros nombres:
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Comparador de placebos: 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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Tabletas de placebo a juego
Otros nombres:
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Comparador de placebos: 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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Tabletas de placebo a juego
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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
Periodo de tiempo: 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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
27 de diciembre de 2012
Finalización primaria (Actual)
28 de marzo de 2017
Finalización del estudio (Actual)
31 de julio de 2017
Fechas de registro del estudio
Enviado por primera vez
19 de diciembre de 2012
Primero enviado que cumplió con los criterios de control de calidad
19 de diciembre de 2012
Publicado por primera vez (Estimar)
24 de diciembre de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
6 de abril de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
12 de marzo de 2021
Última verificación
1 de marzo de 2021
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ARQ197-A-U303
- 2012-003308-10 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .