Clinical trial NCT02150733: Pharmacokinetics of Tivantinib in Subjects With Advanced Solid Tumors and Hepatic Impairment
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Solid Tumor
Cancer
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Medpace, Inc.
First posted: 2014-05-30
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Composite of plasma pharmacokinetic parameters of Tivantinib
timeFrame: 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:
measure: Composite of plasma pharmacokinetic parameters of Tivantinib
timeFrame: 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
measure: Composite of plasma pharmacokinetic parameters of Tivantinib metabolites
timeFrame: 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]
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Hackensack
country: United States
state: New Jersey
Study officials:
affiliation: Daiichi Sankyo
name: Masaya Tachibana, PhD
role: STUDY_DIRECTOR
References: