CompletedNCT02150733Updated Feb 12, 2019

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

A Phase 1 interventional study of Tivantinib and Tivantinib in Hepatic Impairment, Solid Tumor and Cancer, sponsored by Daiichi Sankyo. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-12.

Sponsored by Daiichi Sankyo · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 29
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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.

Conditions studied

Hepatic Impairment
Solid Tumor
Cancer

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Neoplasms 9,610

In context

Neoplasms

9,610 studies on the registry are indexed under Neoplasms; 2,508 are open to participants now.

This study's enrollment of 29 is below the median of 50 across 7,429 interventional studies indexed under Neoplasms.

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Lead sponsor

Daiichi Sankyo is the lead sponsor of 322 studies on the registry; 37 are open to participants now.

Of its 51 completed or terminated interventional studies of FDA-regulated products, 38 (75%) have results posted.

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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
Male or female ≥18 years of age
Life expectancy of >12 weeks
Women of childbearing potential (WOCBP) must have a negative pregnancy test performed prior to the start of study drug
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
Subjects with impaired hepatic function will be grouped according to Child-Pugh classification score
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
Eastern Cooperative Oncology Group (ECOG) performance status ≥2
Adequate bone marrow and renal function
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
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

Exclusion Criteria:

History of liver transplant
Any major surgical procedure within 3 weeks prior to the first dose of study drug;
Active, clinically serious infections defined as ≥Grade 2 according to NCI Common Toxicity Criteria for Adverse Effects (CTCAE), version 4.0
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
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
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
Significant gastrointestinal disorders, in the opinion of the Investigator
Pregnant or breastfeeding
Received Tivantinib as prior therapy
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
Any other investigational drug/medical device within 3 weeks prior to the first dose
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
Subjects receiving Coumadin anticoagulants
Inability to swallow oral medications
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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 29 participants (actual)

Study arms

Experimental
Group 1 - Normal hepatic function
Subjects with normal hepatic function
Drug: Tivantinib
Experimental
Group 2 - Mild hepatic impairment
Subjects with mild hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib
Experimental
Group 3 - Moderate hepatic impairment
Subjects with moderate hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib
Experimental
Group 4 - Severe hepatic impairment
Subjects with severe hepatic impairment by Child-Pugh classification scores
Drug: Tivantinib

Interventions

DrugTivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 360 mg twice daily in the extension phase.
DrugTivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg twice daily in the extension phase
DrugTivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg once daily in the extension phase
DrugTivantinib
Single oral administration of Tivantinib 120 mg on Day 1 followed by Tivantinib 120 mg once every other day in the extension phase

What researchers measure

Primary outcomes

Composite of plasma pharmacokinetic parameters of Tivantinib
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.
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

Secondary outcomes

Composite of plasma pharmacokinetic parameters of Tivantinib
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)
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
Composite of plasma pharmacokinetic parameters of Tivantinib metabolites
The following pharmacokinetic parameters will be determined: Cmax and AUClast, AUCtau, Tmax, and metabolite ratios for Cmax, AUClast, and AUCtau.
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]

Study locations

2 sites

USC/Norris Comprehensive Cancer Center
Los Angeles, California 90033, United States
Hackensack, New Jersey, United States

References and documents

Individual participant data

Plan to share: Yes — 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 information: Study protocol, Statistical analysis plan, Clinical study report

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.

Data sharing details ↗ · vivli.org

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 12, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02150733
Lead sponsor: Daiichi Sankyo
Collaborators: Medpace, Inc.
Responsible party: Sponsor
First posted: May 30, 2014
Start date: Apr 2014
Primary completion: Dec 2015
Completion: Jul 2016
Last update: Feb 12, 2019

Study contacts

Masaya Tachibana, PhD

study director · Daiichi Sankyo

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2016. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: ARQ 197

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