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

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ClinicalTrials.gov Identifier: NCT01755767
Recruitment Status : Completed
First Posted : December 24, 2012
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
ArQule
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE December 19, 2012
First Posted Date  ICMJE December 24, 2012
Last Update Posted Date February 15, 2019
Actual Study Start Date  ICMJE December 27, 2012
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2018)
Rate of Overall Survival (OS) within 36 Months [ Time Frame: within 36 months ]
OS is defined as the time from randomization to the date of death (i.e., the length of time from the start of treatment that patients are still alive). Rate of OS (Percentage of Patients Still Alive) was determined in the Efficacy Analysis Set (only the 120 mg BID Cohort) every 3 months for 36 months.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
Overall survival (OS) in Intent to Treat (ITT) population [ Time Frame: Every 12 weeks ]
Patients will be contacted every 12 weeks to track overall survival
Change History Complete list of historical versions of study NCT01755767 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2018)
Rate of Progression Free Survival (PFS) within 10 months [ Time Frame: within 10 months ]
PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause. Rate of PFS (Percentage of Patients Still Alive without Disease Progression) was determined in the Efficacy Analysis Set (only the 120 mg BID Cohort) every 2 months for 10 months.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2012)
  • Progression free survival (PFS) [ Time Frame: Every 8 weeks ]
    Patients will be evaluated for these endpoints every 8 weeks. Progression free survival (PFS) by central, independent radiology review
  • Safety [ Time Frame: Weekly for first 4 weeks, bi-wekkly thereafter ]
    Further characterize the safety of ARQ 197 in patients with unresectable HCC.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE
  • Drug: Tivantinib
    Tivantinib tablets
    Other Name: ARQ197
  • Drug: Placebo
    Matching placebo tablets
    Other Name: Placebo comparator
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Drug: Tivantinib
  • Experimental: 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).
    Intervention: Drug: Tivantinib
  • Placebo Comparator: 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.
    Intervention: Drug: Placebo
  • Placebo Comparator: 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.
    Intervention: Drug: Placebo
Publications * 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, López López 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 7, 2017)
383
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2012)
303
Actual Study Completion Date  ICMJE March 28, 2017
Actual Primary Completion Date March 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   France,   Germany,   Italy,   Netherlands,   New Zealand,   Portugal,   Spain,   Sweden,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01755767
Other Study ID Numbers  ICMJE ARQ197-A-U303
2012-003308-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE ArQule
Investigators  ICMJE
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
PRS Account Daiichi Sankyo, Inc.
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP