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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Daiichi Sankyo Inc.
Sponsor:
Collaborators:
ArQule
Covance
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01755767
First received: December 19, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Tivantinib
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Overall survival (OS) in Intent to Treat (ITT) population [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
    Patients will be contacted every 12 weeks to track overall survival


Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Patients will be evaluated for these endpoints every 8 weeks. Progression free survival (PFS) by central, independent radiology review

  • Safety [ Time Frame: Throughout treatment and for 30 days after last dose ] [ Designated as safety issue: Yes ]
    Further characterize the safety of ARQ 197 in patients with unresectable HCC.


Estimated Enrollment: 303
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tivantinib Drug: Tivantinib
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.
Other Name: ARQ197
Placebo Comparator: Placebo Drug: Placebo
The control arm will receive matching placebo tablets, once in the morning and once in the evening, with food, continuously.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755767

Contacts
Contact: ArQule, Inc. 800-373-7827 ClinicalTrials@arqule.com

  Show 66 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
ArQule
Covance
Investigators
Study Director: Giovanni Abbadessa, MD ArQule, Inc
  More Information

No publications provided

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01755767     History of Changes
Other Study ID Numbers: ARQ197-A-U303
Study First Received: December 19, 2012
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
MET diagnostic-high
Unresectable
Hepatocellular
Carcinoma
c-Met inhibitor

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on July 22, 2014