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

NCT02150733 | Completed Phase 1

• 1 other identifier: ARQ197-A-U160
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatic Impairment; Solid Tumor; Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (2)

• Composite of plasma pharmacokinetic parameters of Tivantinib

  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

  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 Arms (4)

Group 1 - Normal hepatic function

EXPERIMENTAL

Subjects with normal hepatic function

Drug: Tivantinib

Group 2 - Mild hepatic impairment

EXPERIMENTAL

Subjects with mild hepatic impairment by Child-Pugh classification scores

Drug: Tivantinib

Group 3 - Moderate hepatic impairment

EXPERIMENTAL

Subjects with moderate hepatic impairment by Child-Pugh classification scores

Drug: Tivantinib

Group 4 - Severe hepatic impairment

EXPERIMENTAL

Subjects with severe hepatic impairment by Child-Pugh classification scores

Drug: Tivantinib

Interventions

Tivantinib DRUG

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

Group 1 - Normal hepatic function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Medpace, Inc.: collaborator

Study Sites (2)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Unknown Facility

Hackensack, New Jersey, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

ARQ 197

Study Officials

• Masaya Tachibana, PhD

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 30, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: July 1, 2016
• Last Updated: February 12, 2019

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (2)