AzTrials
AzTrials

Hepatocellular CarcinomaPhase 3METIV-HCCNCT01755767

Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy

A Phase 3 study testing Tivantinib in people with Hepatocellular Carcinoma, run by Daiichi Sankyo at 112 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Tivantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
383 participants
Where
112 sitesin 16 countries
Study dates
27 Dec 2012to 31 Jul 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

112 sites in 16 countries.

112 sites in 16 countries

United States20 sites

  • Study site

    Boston, Massachusetts

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Dallas, Texas

  • Study site

    Detroit, Michigan

  • Study site

    Gainesville, Florida

  • Study site

    Galveston, Texas

  • Study site

    Hackensack, New Jersey

  • Study site

    Houston, Texas

  • Study site

    Los Angeles, California

  • Study site

    Minneapolis, Minnesota

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Orange, California

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Scarborough, Maine

  • Study site

    Seattle, Washington

  • Study site

    Tucson, Arizona

  • Study site

    Washington D.C., District of Columbia

  • Study site

    Westwood, Kansas

Other trials in United States

Germany18 sites

  • Study site

    Aachen

  • Study site

    Berlin

  • Study site

    Bonn

  • Study site

    Düsseldorf

  • Study site

    Essen

  • Study site

    Frankfurt am Main

  • Study site

    Hamburg

  • Study site

    Hanover

  • Study site

    Heidelberg

  • Study site

    Leipzig

  • Study site

    Magdeburg

  • Study site

    Mainz

  • Study site

    München

  • Study site

    Munich

  • Study site

    Regensburg

  • Study site

    Tübingen

  • Study site

    Ulm

  • Study site

    Würzburg

Other trials in Germany

Italy18 sites

  • Study site

    Benevento, 82100

  • Study site

    Bergamo

  • Study site

    Bologna

  • Study site

    Catania

  • Study site

    Florence

  • Study site

    Meldola, Forli-Cesena

  • Study site

    Milan

  • Study site

    Modena

  • Study site

    Naples

  • Study site

    Orbassano (TO), Torino

  • Study site

    Padova

  • Study site

    Parma

  • Study site

    Pavia

  • Study site

    Pisa

  • Study site

    Reggio Emilia

  • Study site

    Roma

  • Study site

    Rozzano, Milano

  • Study site

    Turin

Other trials in Italy

France14 sites

  • Study site

    Amiens

  • Study site

    Bordeaux

  • Study site

    Caen

  • Study site

    Clichy

  • Study site

    Créteil

  • Study site

    Grenoble

  • Study site

    Lille

  • Study site

    Marseille

  • Study site

    Montpellier

  • Study site

    Paris

  • Study site

    Reims

  • Study site

    Rennes

  • Study site

    Toulouse

  • Study site

    Villejuif

Other trials in France

Spain12 sites

  • Study site

    Alicante

  • Study site

    Barcelona

  • Study site

    Córdoba

  • Study site

    Madrid

  • Study site

    Majadahonda, Madrid

  • Study site

    Oviedo, Principality of Asturias

  • Study site

    Pamplona, Navarre

  • Study site

    Sabadell

  • Study site

    Santander

  • Study site

    Santiago de Compostela, A Coruña

  • Study site

    Valencia

  • Study site

    Zaragoza

Other trials in Spain

Australia4 sites

  • Study site

    Camperdown, New South Wales

  • Study site

    Heidelberg, Victoria

  • Study site

    Melbourne, Victoria

  • Study site

    Nedlands, Western Australia

Other trials in Australia

Austria4 sites

  • Study site

    Graz

  • Study site

    Innsbruck

  • Study site

    Linz

  • Study site

    Vienna

Other trials in Austria

Belgium4 sites

  • Study site

    Brussels

  • Study site

    Ghent

  • Study site

    Leuven

  • Study site

    Liège

Other trials in Belgium

Brazil4 sites

  • Study site

    Barretos

  • Study site

    Porto Alegre, Rio Grande do Sul

  • Study site

    Rio de Janeiro

  • Study site

    São Paulo, São Paulo

Other trials in Brazil

Argentina3 sites

  • Study site

    Buenos Aires, Buenos Aires F.D.

  • Study site

    Ciudad Autonoma de Buenos Aires, Buenos Aires

  • Study site

    Pilar

Other trials in Argentina

Portugal3 sites

  • Study site

    Lisbon

  • Study site

    Porto

  • Study site

    Vila Real

Other trials in Portugal

Canada2 sites

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

Other trials in Canada

Sweden2 sites

  • Study site

    Gothenburg

  • Study site

    Stockholm

Other trials in Sweden

Switzerland2 sites

  • Study site

    Bern

  • Study site

    Zurich

Other trials in Switzerland

Netherlands1 site

  • Study site

    Amsterdam

Other trials in Netherlands

New Zealand1 site

  • Study site

    Auckland

Other trials in New Zealand

About this study

Official 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

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.

Read the detailed description

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.

Being tested
Tivantinib, Placebo
Keywords
MET diagnostic-high, Unresectable, Hepatocellular, Carcinoma, c-Met inhibitor
Medical subject headings
Carcinoma, Hepatocellular, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TivantinibDrug

    Also called ARQ197

    Tivantinib tablets

  • PlaceboDrug

    Also called Placebo comparator

    Matching placebo tablets

Study groups in NCT01755767
Study groupRoleWhat they receive
Tivantinib 240 mg BID CohortExperimentalThe 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.
Receives: Drug: Tivantinib
Tivantinib 120 mg BID CohortExperimentalTivantinib 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).
Receives: Drug: Tivantinib
Placebo Matching 240 mg BID CohortPlacebo comparatorMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Receives: Drug: Placebo
Placebo Matching 120 mg BID CohortPlacebo comparatorMatching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: within 36 months

  2. 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.

    Measured: within 36 months

Secondary outcomes (3)

  1. 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)

    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.

    Measured: within 10 months

  2. 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

    Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 120 mg BID cohort group.

    Measured: Baseline to 30 days after last dose, up to approximately 4 years

  3. 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

    Treatment-emergent adverse events (TEAEs) are reported for the tivantinib 240 mg BID cohort group.

    Measured: Baseline to 30 days after last dose, up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2012 (estimated)
  2. Study start27 Dec 2012
  3. Primary completion28 Mar 2017
  4. Study completion31 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
383 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01755767
Sponsor's protocol ID
ARQ197-A-U303
Other IDs
2012-003308-10
Acronym
METIV-HCC
Status last verified
Mar 2021
First submitted
19 Dec 2012
Last updated
6 Apr 2021
Data monitoring committee
Yes
Individual data sharing
No

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.

    PubMed 29625879

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tivantinib in people with Hepatocellular Carcinoma, run by Daiichi Sankyo at 112 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 112 sites in United States, Germany, Italy, France, Spain and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: within 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01755767, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in