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

This study has been completed.
Sponsor:
Collaborators:
ArQule
Covance
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT01755767
First received: December 19, 2012
Last updated: June 7, 2017
Last verified: June 2017
  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
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, 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) [ Time Frame: within 54 months ]
    The length of time from the start of treatment that patients are still alive.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: within 54 months ]
    The length of time from the start of treatment that a patient lives with the disease but it does not get worse.


Enrollment: 383
Study Start Date: December 2012
Study Completion Date: March 28, 2017
Primary Completion Date: March 28, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tivantinib 480 mg
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.
Drug: Tivantinib
Tivantinib tablets
Other Name: ARQ197
Experimental: Tivantinib 240 mg
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).
Drug: Tivantinib
Tivantinib tablets
Other Name: ARQ197
Placebo Comparator: Placebo
Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.
Drug: Placebo
Matching placebo tablets
Other Name: Placebo comparator

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   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • 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
  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

  Show 113 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
ArQule
Covance
Investigators
Study Director: Global Clinical Leader, MD Daiichi Sankyo Inc.
  More Information

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT01755767     History of Changes
Other Study ID Numbers: ARQ197-A-U303
2012-003308-10 ( EudraCT Number )
Study First Received: December 19, 2012
Last Updated: June 7, 2017

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 June 28, 2017