A Two-part Study to Characterize Drug-Drug Interaction Effects on Steady-State Pharmacokinetics of Oral Tazemetostat
Study Details
Study Description
Brief Summary
This is a phase I, multi-center, open-label, multi-dose, two-part PK and safety study to characterize the DDI potential of oral Tazemetostat.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This two-part study is designed to characterize the steady-state PK of oral Tazemetostat and its metabolite EPZ 6930 when administered as a single and twice daily dose in subjects with advanced malignancies while taken alone or in combination with either itraconazole or rifampin.
Part 1: Tazemetostat and Itraconazole Drug Interaction Part 1 of the study will evaluate the drug-drug interaction between Tazemetostat and itraconazole in an open-label, fixed sequential cross over design.
Part 2: Tazemetostat and Rifampin Drug Interaction Part 2 of the study will evaluate the drug-drug interaction between Tazemetostat and rifampin in an open-label, fixed sequential cross over design.
For both Parts 1 and 2, safety and tolerability will be assessed throughout the subject's participation. Subjects must have an end of study visit after 30 days of the last dose of Tazemetostat for safety assessment.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Part 1: Tazemetostat and Itraconazole Drug Interaction Cycle 1 Subjects may discontinue from the study after completion of Cycle 1 or can continue (Cycle 2+ onwards) Tazemetostat treatment at the recommended therapeutic dose (oral 800 mg Tazemetostat twice daily [12 hours apart]) in 28 day cycles. Safety and tolerability will be assessed throughout the subject's participation. |
Drug: Tazemetostat
Physical description: Red, round, and biconvex film-coated tablets packaged in white high-density polyethylene bottle with a child resistant, tamper-evident polypropylene screw cap.
Other Names:
Drug: Itraconazole
During this study, the use of either brand or generic forms of itraconazole is acceptable. Please refer to manufacturer's prescribing information for drug form selected prior to administration.
Other Names:
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Experimental: Part 2:Tazemetostat and Rifampin Drug Interaction Cycle 1 Subjects may discontinue from the study after completion of Cycle 1 or can continue (Cycle 2+ onwards) Tazemetostat treatment at the recommended therapeutic dose (800 mg Tazemetostat twice daily [12 hours apart]), in 28 day cycles. Safety and tolerability will be assessed throughout the subject's participation. |
Drug: Tazemetostat
Physical description: Red, round, and biconvex film-coated tablets packaged in white high-density polyethylene bottle with a child resistant, tamper-evident polypropylene screw cap.
Other Names:
Drug: Rifampin
During this study, the use of either brand or generic forms of rifampin is acceptable. Please refer to manufacturer's prescribing information for drug form selected prior to administration.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Part 1: To evaluate the effect of CYP3A4 inhibition by itraconazole on the steady-state pharmacokinetics (PK) of Tazemetostat when administered as a single and twice daily oral dose in subjects with advanced malignancies, AUC0-t, Cmax [0-72 hours]
- Part 2: To evaluate the effect of CYP3A4 induction by rifampin on the steady-state PK of Tazemetostat when administered as a single and twice daily oral dose in subjects with advanced malignancies, AUC0-t, Cmax. [0-48 hours]
Secondary Outcome Measures
- Part 1: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with itraconazole, and to evaluate the effect of itraconazole on PK of a single 400 mg oral dose of Tazemetostat, AUC0-t. [0-48 hours]
- Part 2: To evaluate the steady-state PK of Tazemetostat and its metabolites after administration alone and with rifampin. [0-48 hours]
- To evaluate the number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0. [Cycle 1, Part 1: Days 1-39 of the 39-day cycle. Cycle 1, Part 2: Days 1-26 of the 26-day cycle. Cycle 2+: Day 1 (±3 days) of every 28-day cycle. End of Study: 30 (±3) days after last dose of study drug. Annual Assessments: Yearly from Day 1 of Cycle 1.]
Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of tazemetostat will be evaluated by the Investigator based on the CTCAE, version 5.0.
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
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Male or female ≥ 18 years age at the time of consent.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
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Has the ability to understand informed consent, and provide signed written informed consent.
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Life expectancy of > 3 months.
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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 hematologic malignancies that have relapsed, or refractory disease, following at least 2 standard lines of systemic therapy for which there are no standard therapies available.
Note: Subjects with prior radiotherapy will be included; however, radiotherapy alone will not be considered a separate systemic treatment regimen.
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Must have evaluable or measurable disease.
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Has all prior treatment (ie, chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 or are clinically stable and not clinically significant, at time of consent.
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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 or 5 half-lives, whichever is shorter may be acceptable.
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Has normal hepatic function (per NCI-ODWG criteria) as well as adequate hematologic (bone marrow [BM] and coagulation factors) and renal function.
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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.
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Females of childbearing potential (FCBP) must have a negative serum pregnancy test and must either practice complete abstinence or agree to use a highly effective method of contraception.
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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 (FCBP) during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.
NOTE: Male subjects must not donate sperm during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation.
- Has a QT interval corrected by Fridericia's formula (QTcF) ≤450 msec.
EXCLUSION CRITERIA:
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Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression or primary glioblastoma multiforme.
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Clinically significant bleeding diathesis or coagulopathy.
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Known hypersensitivity to any of the components of Tazemetostat, itraconazole, or rifampin.
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Use of concurrent investigational agent or anticancer therapy.
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Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
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Have a known active infection with hepatitis B virus (HBV), hepatitis C virus (HCV), AND/OR human T-cell lymphotropic virus 1.
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Subjects taking medications that are known CYP3A4 inducers or inhibitors (including St. John's Wort).
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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.
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Any condition or medical problem in addition to the underlying malignancy and organ dysfunction that the Investigator feels would pose unacceptable risk.
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Has a prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN) or T-cell lymphoblastic lymphoma (T-LBL)/ T-cell acute lymphoblastic leukemia (T-ALL).
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Ingestion of alcohol within 72 hours prior to day 1 of Cycle 1 until the end of Cycle 1 (Day 39 for Part 1 and Day 26 for Part 2). Regular alcohol consumption must not exceed 16 units for males and 7 units for females per week (2 units equals 40mL [a can] of beer, 175mL [a standard glass] of wine, or 50 mL [2 small shots] of spirits
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Any form of marijuana use.
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History of drug abuse (including alcohol) within the last 6 months prior to screening.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | California Cancer Associates for Research and Excellence, Inc. (cCARE) | Encinitas | California | United States | 92024 |
2 | The Angeles Clinic and Research Institute | Los Angeles | California | United States | 90025 |
3 | Northwestern University-Robert H. Lurie Comprehensive Cancer Center | Chicago | Illinois | United States | 60611 |
4 | South Texas Accelerated Research Therapeutics (START) Midwest | Grand Rapids | Michigan | United States | 49546 |
5 | Gabrail Cancer Center | Canton | Ohio | United States | 44718 |
6 | University of Cincinnati Medical Center | Cincinnati | Ohio | United States | 45267 |
7 | Mary Crowley Cancer Research | Dallas | Texas | United States | 75230 |
8 | Onkologikoa | Donostia | Gipuzkoa | Spain | 20014 |
9 | Hospital Universitario Vall d'Hebron | Barcelona | Spain | 08035 | |
10 | Hospital Fundacion Jimenez Diaz | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Epizyme, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EZH-108