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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01755767
Registration number
NCT01755767
Ethics application status
Date submitted
19/12/2012
Date registered
24/12/2012
Titles & IDs
Public title
Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
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Scientific title
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
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Secondary ID [1]
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2012-003308-10
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Secondary ID [2]
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ARQ197-A-U303
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Universal Trial Number (UTN)
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Trial acronym
METIV-HCC
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma
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Condition category
Condition code
Cancer
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Non melanoma skin cancer
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Cancer
0
0
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0
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Kidney
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Cancer
0
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0
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Liver
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Tivantinib
Treatment: Drugs - Placebo
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.
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).
Placebo comparator: 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.
Placebo comparator: 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.
Treatment: Drugs: Tivantinib
Tivantinib tablets
Treatment: Drugs: Placebo
Matching placebo tablets
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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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
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Assessment method [1]
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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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Timepoint [1]
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within 36 months
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Primary outcome [2]
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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
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Assessment method [2]
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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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Timepoint [2]
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within 36 months
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Secondary outcome [1]
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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)
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Assessment method [1]
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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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Timepoint [1]
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within 10 months
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Secondary outcome [2]
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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
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Assessment method [2]
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Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.
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Timepoint [2]
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Baseline to 30 days after last dose, up to approximately 4 years
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Secondary outcome [3]
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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
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Assessment method [3]
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Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.
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Timepoint [3]
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Baseline to 30 days after last dose, up to approximately 4 years
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
27/12/2012
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
31/07/2017
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Sample size
Target
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Accrual to date
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Final
383
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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- Camperdown
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- Heidelberg
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- Melbourne
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- Nedlands
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- Camperdown
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- Heidelberg
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- Melbourne
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- Nedlands
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Daiichi Sankyo
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
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Ethics approval
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT01755767
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Trial related presentations / publications
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.
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Public notes
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Contacts
Principal investigator
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Global Clinical Leader
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Daiichi Sankyo
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Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
Query!
No/undecided IPD sharing reason/comment
Query!
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Study protocol
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/67/NCT01755767/Prot_SAP_000.pdf
Statistical analysis plan
Study Protocol and Statistical Analysis Plan
https://cdn.clinicaltrials.gov/large-docs/67/NCT01755767/Prot_SAP_000.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT01755767