Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
METIV-HCC
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
2 other identifiers
interventional
383
15 countries
108
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 hepatocellular-carcinoma
Started Dec 2012
Typical duration for phase_3 hepatocellular-carcinoma
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 19, 2012
CompletedFirst Posted
Study publicly available on registry
December 24, 2012
CompletedStudy Start
First participant enrolled
December 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2017
CompletedResults Posted
Study results publicly available
July 15, 2020
CompletedApril 6, 2021
March 1, 2021
4.3 years
December 19, 2012
June 10, 2020
March 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
within 36 months
Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Overall survival (OS) is defined as the time from randomization to the date of death. The rate of OS (percentage of participants still alive) was determined only in the tivantinib 120 mg BID cohort.
within 36 months
Secondary Outcomes (3)
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)
within 10 months
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Baseline to 30 days after last dose, up to approximately 4 years
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Baseline to 30 days after last dose, up to approximately 4 years
Study Arms (4)
Tivantinib 240 mg BID Cohort
EXPERIMENTALThe 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.
Tivantinib 120 mg BID Cohort
EXPERIMENTALTivantinib 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).
Placebo Matching 240 mg BID Cohort
PLACEBO COMPARATORMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Placebo Matching 120 mg BID Cohort
PLACEBO COMPARATORMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Interventions
Tivantinib tablets
Matching placebo tablets
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (112)
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Tucson, Arizona, United States
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Los Angeles, California, United States
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Orange, California, United States
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Washington D.C., District of Columbia, United States
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Gainesville, Florida, United States
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Chicago, Illinois, United States
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Westwood, Kansas, United States
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New Orleans, Louisiana, United States
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Scarborough, Maine, United States
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Boston, Massachusetts, United States
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Detroit, Michigan, United States
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Minneapolis, Minnesota, United States
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Hackensack, New Jersey, United States
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New York, New York, United States
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Philadelphia, Pennsylvania, United States
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Charleston, South Carolina, United States
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Dallas, Texas, United States
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Galveston, Texas, United States
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Houston, Texas, United States
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Seattle, Washington, United States
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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
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Buenos Aires, Buenos Aires F.D., Argentina
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Pilar, Argentina
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Camperdown, New South Wales, Australia
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Heidelberg, Victoria, Australia
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Melbourne, Victoria, 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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Vienna, Austria
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Brussels, Belgium
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Ghent, Belgium
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Leuven, Belgium
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Liège, Belgium
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Porto Alegre, Rio Grande do Sul, Brazil
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São Paulo, São Paulo, Brazil
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Barretos, Brazil
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Rio de Janeiro, Brazil
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Vancouver, British Columbia, Canada
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Toronto, Ontario, Canada
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Amiens, France
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Bordeaux, France
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Caen, France
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Clichy, France
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Créteil, France
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Grenoble, France
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Lille, France
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Marseille, France
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Montpellier, France
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Paris, France
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Reims, France
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Rennes, France
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Toulouse, France
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Villejuif, France
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Aachen, Germany
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Berlin, Germany
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Bonn, Germany
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Düsseldorf, Germany
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Essen, Germany
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Frankfurt am Main, Germany
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Hamburg, Germany
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Hanover, Germany
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Heidelberg, Germany
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Leipzig, Germany
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Magdeburg, Germany
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Mainz, Germany
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Munich, Germany
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München, Germany
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Regensburg, Germany
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Tübingen, Germany
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Ulm, Germany
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Würzburg, Germany
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Meldola, Forli-Cesena, Italy
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Rozzano, Milano, Italy
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Orbassano (TO), Torino, Italy
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Benevento, 82100, Italy
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Bergamo, Italy
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Bologna, Italy
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Catania, Italy
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Florence, Italy
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Milan, Italy
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Modena, Italy
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Napoli, Italy
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Padua, Italy
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Parma, Italy
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Pavia, Italy
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Pisa, Italy
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Reggio Emilia, Italy
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Roma, Italy
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Turin, Italy
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Amsterdam, Netherlands
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Auckland, New Zealand
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Lisbon, Portugal
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Porto, Portugal
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Vila Real, Portugal
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Santiago de Compostela, A Coruña, Spain
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Majadahonda, Madrid, Spain
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Pamplona, Navarre, Spain
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Oviedo, Principality of Asturias, Spain
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Alicante, Spain
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Barcelona, Spain
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Córdoba, Spain
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Madrid, Spain
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Sabadell, Spain
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Santander, Spain
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Valencia, Spain
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Zaragoza, Spain
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Gothenburg, Sweden
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Stockholm, Sweden
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Bern, Switzerland
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Zurich, Switzerland
Related Publications (1)
Rimassa L, Assenat E, Peck-Radosavljevic M, Pracht M, Zagonel V, Mathurin P, Rota Caremoli E, Porta C, Daniele B, Bolondi L, Mazzaferro V, Harris W, Damjanov N, Pastorelli D, Reig M, Knox J, Negri F, Trojan J, Lopez Lopez C, Personeni N, Decaens T, Dupuy M, Sieghart W, Abbadessa G, Schwartz B, Lamar M, Goldberg T, Shuster D, Santoro A, Bruix J. Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study. Lancet Oncol. 2018 May;19(5):682-693. doi: 10.1016/S1470-2045(18)30146-3. Epub 2018 Apr 3.
PMID: 29625879DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Contact for Clinical Trial Information
- Organization
- Daiichi Sankyo
Study Officials
- STUDY DIRECTOR
Global Clinical Leader
Daiichi Sankyo
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 19, 2012
First Posted
December 24, 2012
Study Start
December 27, 2012
Primary Completion
March 28, 2017
Study Completion
July 31, 2017
Last Updated
April 6, 2021
Results First Posted
July 15, 2020
Record last verified: 2021-03
Data Sharing
- IPD Sharing
- Will not share