A Study of Oral Tazemetostat in Subjects With Moderate and Severe Hepatic Impairment With Advanced Malignancies

  • STATUS
    Recruiting
  • End date
    Jul 22, 2022
  • participants needed
    24
  • sponsor
    Epizyme, Inc.
Updated on 22 November 2021
antibiotics
renal function
cancer
hematologic malignancy
lymphoma
serum pregnancy test
measurable disease
solid tumour
oral contraception
malabsorption syndrome

Summary

This is a phase 1, 2-part, global, multicenter, open-label, PK, safety and tolerability study of oral tazemetostat in subjects with either advanced solid tumors, or hematological malignancies and normal hepatic function or moderate, or severe hepatic impairment.

Description

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 after 30 days of the last dose of tazemetostat for safety assessment. 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.

Details
Condition Advanced Solid Tumor, Hepatic Impairment, Advanced Malignant Solid Tumor
Treatment Tazemetostat
Clinical Study IdentifierNCT04241835
SponsorEpizyme, Inc.
Last Modified on22 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female 18 years age at the time of consent
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Has the ability to understand informed consent and provided signed written informed consent
Life expectancy of > 3 months
Histologically and/or cytologically confirmed advanced metastatic or unresectable solid tumors has progressed after treatment for which there are no standard therapies available OR histologically and/or cytologically confirmed hematological malignancies that have relapsed, or refractory disease following at least 2 standard lines of systemic therapy for which there are no standard therapies available
Must have evaluable or measurable disease
Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to Grade 1 per NCI CTCAE, Version 5.0 or are clinically stable and not clinically significant, at time of consent
All subjects must have completed any prior chemotherapy, targeted therapy and major surgery, 28 days before study entry. For daily or weekly chemotherapy without the potential for delayed toxicity, a washout period of 14 days may be acceptable, and questions related to this can be discussed with the Medical Monitor
Has adequate hematologic (bone marrow [BM] and coagulation factors), and renal function
Able to swallow and retain orally-administered medication and without clinically significant gastrointestinal abnormalities that could alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
Subjects with abnormal hepatic function will be eligible and will be grouped according to established criteria. Subjects with active hemolysis will be excluded
Manual differential with no significant morphologic abnormalities on complete blood count (CBC) testing
Male subjects must have had a successful vasectomy OR must either practice complete abstinence or agree to use a latex or synthetic condom during sexual contact with a female of childbearing potential from the first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation
Females of childbearing potential must have a negative serum pregnancy test at screening and within 24 hours prior to the first dose of study drug. All females will be considered of childbearing potential unless they are naturally postmenopausal or have been sterilized
Females of childbearing potential (FCBP) must either practice complete abstinence or agree to use a highly effective method of contraception beginning at least 28 days prior to the first dose of study drug, during study treatment (including during dose interruptions), and for 6 months after study drug discontinuation
Has a QT interval corrected by Fridericia's formula (QTcF) 480 msec
Subjects with diagnosed human immunodeficiency virus (HIV) are eligible to participate in the study if they meet established criteria

Exclusion Criteria

Prior exposure to tazemetostat or other inhibitor(s) of EZH2
Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam. Subject's with primary glioblastoma multiforme are excluded
Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders. Subjects on anticoagulation with low molecular weight heparin are allowed
Known hypersensitivity to any of the components of tazemetostat
Concurrent investigational agent or anticancer therapy. NOTE: Megestrol (Megace) if used as an appetite stimulant is allowed
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements
Have a known active infection with hepatitis B virus (HBV, as measured by positive hepatitis B surface antigen, hepatitis C virus (HCV, as measured by positive hepatitis C antibody), OR human T-cell lymphotropic virus 1
Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort)
Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from 24 hours prior to the first dose of study drug until the last dose of study drug
Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the Investigator feels would pose unacceptable risk
Has thrombocytopenia, neutropenia, or anemia of grade 3 (per CTCAE 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)
Has abnormalities known to be associated with MDS and multiple primary neoplasms (MPN) observed in cytogenetic testing and DNA sequencing
Has a prior history of T-LBL/T-ALL
Ingestion of alcohol and smoking is not permitted any time during the study
History of drug abuse (including alcohol) within the last 6 months prior to screening
Severe hepatic encephalopathy (Grade >2) or degree of CNS impairment which the Investigator considers sufficiently serious to interfere with the informed consent, the conduct, the completion, or the results of this trial, or constitutes an unacceptable risk to the subject
History of liver transplantation
Advanced ascites or ascites that require drainage and albumin supplementation, as judged by the Investigator
Acute damage of the liver with Grade 4 AST/ALT values at screening or admission
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