This main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the study drug tazemetostat. The pharmacokinetics of the study drug in participants with advanced solid tumors and moderate or severe hepatic (liver) impairment will be compared with participants with advanced malignancies and normal hepatic function. An advanced malignancy is a cancer that has recurred (come back) after prior treatment or hasn't controlled with treatment. The trial will also study the safety of the study drug in participants (how well it is tolerated).
The study will be conducted in 2 parts for subjects with advanced malignancies and either normal liver function, or advanced malignancies and moderate, or severe hepatic impairment. Subjects in Part 1 of the study will receive a single oral, 800 mg dose of tazemetostat on Day 1 and Day 15. In addition, the subjects will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily from Day 5 to Day 14. Blood samples for PK analysis will be obtained on Day 1 through Day 4 and again on Day 15 through Day 18. Part 1 ends on Day 18. Subjects continuing treatment in Part 2 will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily in repeated 28-day cycles beginning on Day 19 until Investigator-assessed clinical progression per standard practice, or unacceptable toxicity, or until another discontinuation criterion is met. Subjects must have an end of study visit for safety assessment 30 days after the last dose of tazemetostat or prior to initiation of a subsequent anticancer therapy, whichever occurs first. Supplementary study conduct information not mandated to be present in this protocol is provided in the accompanying procedure manuals (i.e., laboratory, pharmacy, ECG manuals). Such manuals will provide the site personnel with administrative and detailed technical information that does not impact subject safety.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Tazemetostat (EPZ-6438) in tablet form at a dose of 800 mg once daily on days 1 and 15 and twice daily on days 5 to 14 of the first 28-day cycle. Participants may continue tazemetostat treatment at 800 mg twice daily in additional 28-day cycles until progression or unacceptable toxicity.
Florida Cancer Specialists & Research Institute
Lake Mary, Florida, United States
COMPLETEDRobert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
COMPLETEDHematology Oncology Consultants
Royal Oak, Michigan, United States
COMPLETEDComprehensive Cancer Center of Nevada
Las Vegas, Nevada, United States
COMPLETEDRutgers Cancer Institute
New Brunswick, New Jersey, United States
RECRUITINGGabrail Cancer Center
Canton, Ohio, United States
COMPLETEDMary Crowley Cancer Research
Dallas, Texas, United States
COMPLETEDOncology Consultants - Texas Medical Center
Houston, Texas, United States
WITHDRAWNVirginia Cancer Specialists
Fairfax, Virginia, United States
RECRUITINGAntwerp University Hospital
Edegem, Antwerp, Belgium
TERMINATED...and 8 more locations
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-t: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function.
Time frame: 0 to 72 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-∞: area under the plasma concentration-time curve from time 0 extrapolated to infinity
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function
Time frame: 0 to 72 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, AUC0-8: area under the plasma concentration-time curve from time 0 to 8 hours post dose
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with participants with advanced malignancies and normal hepatic function
Time frame: 0 to 8 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Cmax: observed maximum plasma concentration
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Time frame: 0 to 72 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, Tmax: observed time at Cmax
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Time frame: 0 to 72 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, t1/2: terminal elimination half-life
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Time frame: 0 to 72 hours post dose on Day 1 and Day 15
To evaluate the pharmacokinetics (PK) of tazemetostat and its metabolite EPZ 6930, fu: unbound fraction of drug in plasma
When administered as a single and multi-dose in subjects with advanced malignancies and moderate or severe hepatic impairment, compared with subjects with advanced malignancies and normal hepatic function
Time frame: Pre-dose, 3 hours, 24 hours, and 72 hours post-dose
To evaluate the number of participants with adverse events (AEs) as assessed by CTCAE v5.0
Severity of adverse events experienced by all participants with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0
Time frame: Through study completion, an average of 1 year
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