This trial is active, not recruiting.

Condition hepatocellular carcinoma
Treatments tivantinib, placebo
Phase phase 3
Target c-MET
Sponsor Daiichi Sankyo Inc.
Collaborator ArQule
Start date December 2012
End date March 2017
Trial size 368 participants
Trial identifier NCT01755767, ARQ197-A-U303


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
tivantinib ARQ197
The tivantinib dosage of 120 mg administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 240 mg.
(Placebo Comparator)
The control arm will receive matching placebo tablets, once in the morning and once in the evening, with food, continuously.

Primary Outcomes

Overall survival (OS) in Intent to Treat (ITT) population
time frame: Every 12 weeks

Secondary Outcomes

Progression free survival (PFS)
time frame: Every 8 weeks
time frame: Throughout treatment and for 30 days after last dose

Eligibility Criteria

Male or female participants at least 18 years old.

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 - ECOG Performance Status (PS) of <= equal to 1 - 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. Tumor lesions previously treated with local therapy should demonstrate clear dimensional increase by radiographic assessment in order to be selected as target lesion(s) at baseline. - Adequate bone marrow, liver, and renal functions at Screening Visit, defined as: platelet count greater than or equal to 60 x 10^9/L; hemoglobin greater than or equal to 9.0 g/dL; absolute neutrophil count (ANC) <= 1.5 x 10^9/L; total bilirubin <= 2 mg/dL; Alanine transaminase (ALT) and aspartate aminotransferase (AST) <= 5 x upper limit of normal (ULN); serum creatinine <= 1.5 x ULN; albumin <= 2.8 g/dL; international normalized ratio (INR) 0.8 to ULN or <= 3 for subjects receiving anticoagulant such as coumadin or heparin. Subjects who are therapeutically anticoagulated are allowed to participate provided that prior to anticoagulant therapy no evidence of underlying defect in coagulation exists - Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the randomization (where demanded by local regulations, test may be required within 72 hours prior to randomization) - Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received - Life expectancy of at least 12 weeks 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 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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Daiichi Sankyo Inc..
Location data was received from the National Cancer Institute and was last updated in January 2016.