Clinical trial NCT01755767: Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: MET diagnostic-high
Unresectable
Hepatocellular
Carcinoma
c-Met inhibitor
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
First posted: 2012-12-24
Enrollment: 383
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: within 36 months
measure: 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
timeFrame: within 36 months
Secondary outcomes:
measure: 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)
timeFrame: within 10 months
measure: 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
timeFrame: Baseline to 30 days after last dose, up to approximately 4 years
measure: 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
timeFrame: Baseline to 30 days after last dose, up to approximately 4 years
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Westwood
country: United States
state: Kansas
city: New Orleans
country: United States
state: Louisiana
city: Scarborough
country: United States
state: Maine
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Ciudad Autonoma de Buenos Aires
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Caba
city: Pilar
country: Argentina
city: Camperdown
country: Australia
state: New South Wales
city: Heidelberg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Ghent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Porto Alegre
country: Brazil
state: RS
city: Sao Paulo
country: Brazil
state: SP
city: Barretos
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Amiens Cedex 1
country: France
city: Bordeaux Cedex
country: France
city: Caen Cedex 09
country: France
city: Clichy
country: France
city: Creteil
country: France
city: Grenoble
country: France
city: Lille Cedex
country: France
city: Marseille Cedex 09
country: France
city: Montpellier
country: France
city: Paris Cedex 12
country: France
city: Paris Cedex
country: France
city: Reims Cedex
country: France
city: Rennes Cedex
country: France
city: Toulouse Cedex 09
country: France
city: Villejuif Cedex
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Duesseldorf
country: Germany
city: Essen
country: Germany
city: Frankfurt am Main
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Leipzig
country: Germany
city: Magdeburg
country: Germany
city: Mainz
country: Germany
city: Muenchen
country: Germany
city: Munich
country: Germany
city: Regensburg
country: Germany
city: Tuebingen
country: Germany
city: Ulm
country: Germany
city: Wuerzburg
country: Germany
city: Meldola
country: Italy
state: Forli-Cesena
city: Rozzano
country: Italy
state: Milano
city: Orbassano (TO)
country: Italy
state: Torino
city: Benevento
country: Italy
city: Bergamo
country: Italy
city: Bologna
country: Italy
city: Catania
country: Italy
city: Firenze
country: Italy
city: Milano
country: Italy
city: Modena
country: Italy
city: Napoli
country: Italy
city: Padova
country: Italy
city: Parma
country: Italy
city: Pavia
country: Italy
city: Pisa
country: Italy
city: Reggio Emilia
country: Italy
city: Roma
country: Italy
city: Turin
country: Italy
city: Amsterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Vila Real
country: Portugal
city: Santiago de Compostela
country: Spain
state: A Coruña
city: Oviedo
country: Spain
state: Asturias
city: Majadahonda
country: Spain
state: Madrid
city: Pamplona
country: Spain
state: Navarra
city: Alicante
country: Spain
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Sabadell
country: Spain
city: Santander
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Gothenburg
country: Sweden
city: Stockholm
country: Sweden
city: Bern
country: Switzerland
city: Zurich
country: Switzerland
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References:
citation: 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.