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Pharmacokinetics of Tivantinib in Subjects With Advanced Solid Tumors and Hepatic Impairment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02150733
Recruitment Status : Completed
First Posted : May 30, 2014
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
Medpace, Inc.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This is a multi-center, open-label, Phase 1 study to evaluate the impact of hepatic impairment on the pharmacokinetics of Tivantinib in cancer subjects with varying degrees of hepatic function, from normal to severely impaired.

Condition or disease Intervention/treatment Phase
Hepatic Impairment Solid Tumor Cancer Drug: Tivantinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label Study Assessing the Impact of Hepatic Impairment on the Pharmacokinetics of Tivantinib in Subjects With Advanced Solid Tumors
Study Start Date : April 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : July 2016

Arm Intervention/treatment
Experimental: Group 1 - Normal hepatic function
Subjects with normal hepatic function
Drug: Tivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 360 mg twice daily in the extension phase.

Experimental: Group 2 - Mild hepatic impairment
Subjects with mild hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg twice daily in the extension phase

Experimental: Group 3 - Moderate hepatic impairment
Subjects with moderate hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg once daily in the extension phase

Experimental: Group 4 - Severe hepatic impairment
Subjects with severe hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg once every other day in the extension phase




Primary Outcome Measures :
  1. Composite of plasma pharmacokinetic parameters of Tivantinib [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose ]
    The following pharmacokinetic parameters will be determined: population estimates of apparent total clearance (CL/F), apparent volume of distribution (V/F), area under the concentration-time curve during the dosing interval (AUCtau), and maximum concentration (Cmax) during the dosing interval.


Secondary Outcome Measures :
  1. Composite of plasma pharmacokinetic parameters of Tivantinib [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose ]
    The following pharmacokinetic parameters will be determined: area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast) and Cmax after single dose, time to maximum plasma concentration (Tmax)

  2. Composite of plasma pharmacokinetic parameters of Tivantinib metabolites [ Time Frame: 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours after a single dose and 0 (predose), 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after Cycle 1 Day 11 dose] ]
    The following pharmacokinetic parameters will be determined: Cmax and AUClast, AUCtau, Tmax, and metabolite ratios for Cmax, AUClast, and AUCtau.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must have histologically or cytologically confirmed advanced solid tumor. However, Hepatocellular Carcinoma (HCC) subjects are allowed without histological confirmation as long as there is radiological diagnosis as per standard criteria
  2. Male or female ≥18 years of age
  3. Life expectancy of >12 weeks
  4. Women of childbearing potential (WOCBP) must have a negative pregnancy test performed prior to the start of study drug
  5. Male subjects and WOCBP must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug
  6. Subjects with impaired hepatic function will be grouped according to Child-Pugh classification score
  7. Subjects with biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent has been in place for at least 10 days prior to the first dose of Tivantinib, and the subject's liver function has stabilized as defined by 2 measurements at least 5 days apart that put the subject in the same hepatic impairment group
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≥2
  9. Adequate bone marrow and renal function
  10. Ability to provide written informed consent, comply with protocol visits and procedures, take oral medication, and not have any active infection or chronic comorbidity that would interfere with therapy
  11. Fully informed about their illness and the investigational nature of the study protocol and must sign and date an Institutional Review Board-approved Informed Consent Form

Exclusion Criteria:

  1. History of liver transplant
  2. Any major surgical procedure within 3 weeks prior to the first dose of study drug;
  3. Active, clinically serious infections defined as ≥Grade 2 according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0
  4. Known metastatic brain or meningeal tumors, unless the subject is >3 months from definitive therapy and clinically stable (supportive therapy with steroids or anticonvulsant medications is allowed) with respect to the tumor at the time of the first dose of study drug
  5. History of cardiac disease

    • Active coronary artery disease, defined as myocardial infarction, unstable angina, coronary bypass graft, or stenting within 6 months prior to study entry
    • Evidence of uncontrolled bradycardia or other cardiac arrhythmia defined as ≥Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertension
  6. Any condition that is unstable or that could jeopardize the safety of the subject and the subject's protocol compliance, including known infection with human immunodeficiency virus
  7. Significant gastrointestinal disorders, in the opinion of the Investigator
  8. Pregnant or breastfeeding
  9. Received Tivantinib as prior therapy
  10. Received anti-cancer therapy, including antibody, retinoid, or hormonal treatment (except megestrol acetate as supportive care), and radiation, within 3 weeks before dosing. Prior and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin and analogs for neuroendocrine tumors are permitted
  11. Any other investigational drug/medical device within 3 weeks prior to the first dose
  12. Substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the subject's participation in the clinical study or evaluation of the clinical study results
  13. Subjects receiving Coumadin anticoagulants
  14. Inability to swallow oral medications
  15. Administration or possibility of initiating or continuing any treatment with any known Cytochrome P450 3A4 (CYP3A4) and CYP2C19 enzyme and P-glycoprotein altering drugs (inducer or inhibitor) or non drug agents within 14 days prior to dosing and during the primary objective phase

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02150733


Locations
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United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, New Jersey
Hackensack, New Jersey, United States
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Medpace, Inc.
Investigators
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Study Director: Masaya Tachibana, PhD Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02150733    
Other Study ID Numbers: ARQ197-A-U160
First Posted: May 30, 2014    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/
Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases