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

NCT ID: NCT01755767

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 383 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-27
• Study Completion Date: 2017-07-31

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tivantinib

Intervention Type: DRUG

Tivantinib tablets

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).

Group Type: EXPERIMENTAL

Tivantinib

Intervention Type: DRUG

Tivantinib tablets

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets

Interventions

Tivantinib

Tivantinib tablets

Intervention Type: DRUG

Placebo

Matching placebo tablets

Intervention Type: DRUG

Other Intervention Names

ARQ197; Placebo comparator

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Leader

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Tucson, Arizona, United States

Los Angeles, California, United States

Orange, California, United States

Washington D.C., District of Columbia, United States

Gainesville, Florida, United States

Chicago, Illinois, United States

Westwood, Kansas, United States

New Orleans, Louisiana, United States

Scarborough, Maine, United States

Boston, Massachusetts, United States

Detroit, Michigan, United States

Minneapolis, Minnesota, United States

Hackensack, New Jersey, United States

New York, New York, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Dallas, Texas, United States

Galveston, Texas, United States

Houston, Texas, United States

Seattle, Washington, United States

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Buenos Aires, Buenos Aires F.D., Argentina

Pilar, , Argentina

Camperdown, New South Wales, Australia

Heidelberg, Victoria, Australia

Melbourne, Victoria, Australia

Nedlands, Western Australia, Australia

Graz, , Austria

Innsbruck, , Austria

Linz, , Austria

Vienna, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Liège, , Belgium

Porto Alegre, Rio Grande do Sul, Brazil

São Paulo, São Paulo, Brazil

Barretos, , Brazil

Rio de Janeiro, , Brazil

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Amiens, , France

Bordeaux, , France

Caen, , France

Clichy, , France

Créteil, , France

Grenoble, , France

Lille, , France

Marseille, , France

Montpellier, , France

Paris, , France

Reims, , France

Rennes, , France

Toulouse, , France

Villejuif, , France

Aachen, , Germany

Berlin, , Germany

Bonn, , Germany

Düsseldorf, , Germany

Essen, , Germany

Frankfurt am Main, , Germany

Hamburg, , Germany

Hanover, , Germany

Heidelberg, , Germany

Leipzig, , Germany

Magdeburg, , Germany

Mainz, , Germany

Munich, , Germany

München, , Germany

Regensburg, , Germany

Tübingen, , Germany

Ulm, , Germany

Würzburg, , Germany

Meldola, Forli-Cesena, Italy

Rozzano, Milano, Italy

Orbassano (TO), Torino, Italy

Benevento, , Italy

Bergamo, , Italy

Bologna, , Italy

Catania, , Italy

Florence, , Italy

Milan, , Italy

Modena, , Italy

Napoli, , Italy

Padua, , Italy

Parma, , Italy

Pavia, , Italy

Pisa, , Italy

Reggio Emilia, , Italy

Roma, , Italy

Turin, , Italy

Amsterdam, , Netherlands

Auckland, , New Zealand

Lisbon, , Portugal

Porto, , Portugal

Vila Real, , Portugal

Santiago de Compostela, A Coruña, Spain

Majadahonda, Madrid, Spain

Pamplona, Navarre, Spain

Oviedo, Principality of Asturias, Spain

Alicante, , Spain

Barcelona, , Spain

Córdoba, , Spain

Madrid, , Spain

Sabadell, , Spain

Santander, , Spain

Valencia, , Spain

Zaragoza, , Spain

Gothenburg, , Sweden

Stockholm, , Sweden

Bern, , Switzerland

Zurich, , Switzerland

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; France; Germany; Italy; Netherlands; New Zealand; Portugal; Spain; Sweden; Switzerland

References

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.

Reference Type: DERIVED

PMID: 29625879 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2012-003308-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ARQ197-A-U303

Identifier Type: -

Identifier Source: org_study_id