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All MalignanciesPhase 1NCT04537715

Effects of Itraconazole and Rifampin on the Blood Tazemetostat Levels

A Phase 1 study testing Tazemetostat, Itraconazole and Rifampin in people with All Malignancies and Advanced Malignancies, run by Epizyme, Inc. at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The participants of this study will have advanced malignancies (also known as advanced cancer). The main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the tazemtostat (the study drug) when administered in combination with another drug. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat, Itraconazole and Rifampin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
10 sitesin 2 countries
Study dates
23 Apr 2020to 3 Apr 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 provide 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 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.
  • 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.
  • 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.
  • Has normal hepatic function (per NCI-ODWG criteria) as well as 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.
  • 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.
  • 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.

Who cannot join

  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression or primary glioblastoma multiforme.
  • Clinically significant bleeding diathesis or coagulopathy.
  • Known hypersensitivity to any of the components of Tazemetostat, itraconazole, or rifampin.
  • Use of concurrent investigational agent or anticancer therapy.
  • 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.
  • 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).
  • 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 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).
  • 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
  • Any form of marijuana use.
  • History of drug abuse (including alcohol) within the last 6 months prior to screening.

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

United States7 sites

  • Gabrail Cancer Center

    Canton, Ohio, 44718

  • Northwestern University-Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

  • Mary Crowley Cancer Research

    Dallas, Texas, 75230

  • California Cancer Associates for Research and Excellence, Inc. (cCARE)

    Encinitas, California, 92024

  • South Texas Accelerated Research Therapeutics (START) Midwest

    Grand Rapids, Michigan, 49546

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

Other trials in United States

Spain3 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Onkologikoa

    Donostia / San Sebastian, Gipuzkoa, 20014

  • Hospital Fundacion Jimenez Diaz

    Madrid, 28040

Other trials in Spain

About this study

Official title: A Phase I, Open-label Multi-dose Two-part Study to Characterize the Effects of a Strong CYP3A4 Inhibitor and a Strong CYP3A4 Inducer on the Steady-State Pharmacokinetics of Tazemetostat (EPZ-6438) in Subjects With Advanced Malignancies

The participants of this study will have advanced malignancies (also known as advanced cancer). The main aim of this trial will be to study the blood levels (known as pharmacokinetics) of the tazemtostat (the study drug) when administered in combination with another drug.

Part 1 of the study will evaluate the interaction between the drugs tazemetostat and itraconazole.

Part 2 of the study will evaluate the interaction between the drugs tazemetostat and rifampin

For both Parts 1 and 2, safety and the level that effects of the study drug can be tolerated (known as tolerability) will be assessed throughout.

Read the 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.

Being tested
Tazemetostat, Itraconazole, Rifampin
Keywords
Epizyme, Tazverik, Tazemetostat (EPZ-6438), Itraconazole, CYP3A4 inhibitor, Rifampin, CYP3A4 inducer, Drug-Drug Interaction (DDI), Pharmacokinetics (PK)
Medical subject headings
Hematologic Neoplasms, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Sarcoma, Sarcoma, Synovial, Mesothelioma, Rhabdoid Tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TazemetostatDrug

    Also called EPZ-6438, Tazverik

    A single, oral, 400 mg dose of tazemetostat on Day 1, Day 15, and Day 36; and tazemetostat (oral 400 mg) tablets twice daily on Days 3 - 14 and Days 21 - 35.

  • ItraconazoleDrug

    Also called Sporanox

    Oral 200 mg itraconazole once daily on Days 18 - 38

  • TazemetostatDrug

    Also called EPZ-6438, Tazverik

    A single, oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 24 ; and tazemetostat (oral 800 mg) twice daily on Days 3 - 14 and on Days 17 - 23.

  • RifampinDrug

    Also called RIF, Rifampicin, Rifadin, Rimactane

    Oral 600 mg rifampin once daily on Days 17 - 25.

Study groups in NCT04537715
Study groupRoleWhat they receive
Part 1: Tazemetostat and Itraconazole Drug Interaction Cycle 1ExperimentalParticipants in Part 1 of the study will receive a single oral, 400 mg dose of tazemetostat on Day 1, 15, and Day 36. The study participants will receive tazemetostat (oral 400 mg) tablets to be taken twice daily on Days 3 - 14 and Days 21 - 35. In addition, the participants will receive oral 200 mg itraconazole once daily on Days 18 - 38. Study participants may continue tazemetostat from Day 40+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.
Receives: Drug: Tazemetostat; Drug: Itraconazole
Part 2:Tazemetostat and Rifampin Drug Interaction Cycle 1ExperimentalParticipants in Part 2 of the study will receive a single oral, 800 mg dose of tazemetostat on Days 1, 15, and Day 36. The study participants will receive tazemetostat (oral 800 mg dose) tablets to be taken twice daily on Days 3 - 14 and Days 17 - 23. In addition, the participants will receive oral 200 mg rifampin once daily on Days 17 - 25. Study participants may continue tazemetostat from Day 27+ at the recommended therapeutic dose (oral 800 mg twice daily) in 28-day cycles.
Receives: Drug: Tazemetostat; Drug: Rifampin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours of Quantifiable Concentration (AUC0-12h) of Tazemetostat

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15

  2. Part 1: Maximum Observed Plasma Concentration (Cmax) of Tazemetostat

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, 48, and 72 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15

  3. Part 2: AUC0-12h of Tazemetostat

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15

  4. Part 2: Cmax of Tazemetostat

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15

Secondary outcomes (16)

  1. Part 1: AUC0-12h of EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 15

  2. Part 1: AUC0-12h of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 36

  3. Part 1: Cmax of EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15

  4. Part 1: Cmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady State With Itraconazole

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36

  5. Part 1: Observed Time at Cmax (Tmax) of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15

  6. Part 1: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole

    Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36

  7. Part 1: Apparent Terminal Elimination Half-Life (t1/2) of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 15

  8. Part 1: T1/2 of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Itraconazole

    Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 36, and 72 hours post-dose on Cycle 1 Day 36

  9. Part 2: AUC0-12h of EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 15

  10. Part 2: AUC0-12h of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin

    Blood samples were collected at specified timepoints. AUC0-12h was assessed using non-compartmental data analysis method. AUC0-12h was estimated by a combination of linear trapezoidal method on concentrations going up and logarithmic trapezoidal method on concentrations going down (Linear up/Log down method).

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Cycle 1 Day 24

  11. Part 2: Cmax of EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15

  12. Part 2: Cmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady State With Rifampin

    Blood samples were collected at specified timepoints. Cmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24

  13. Part 2: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15

  14. Part 2: Tmax of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin

    Blood samples were collected at specified timepoints. Tmax was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24

  15. Part 2: T1/2 of Tazemetostat and EPZ-6930 EPZ-6930 After Tazemetostat Alone at Steady-State

    Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours post-dose on Cycle 1 Day 15

  16. Part 2: T1/2 of Tazemetostat and EPZ-6930 After Tazemetostat at Steady-State With Rifampin

    Blood samples were collected at specified timepoints. T1/2 was assessed using non-compartmental data analysis method.

    Measured: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours post-dose on Cycle 1 Day 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2020
  2. Study start23 Apr 2020
  3. Primary completion3 Apr 2023
  4. Study completion3 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04537715
Sponsor's protocol ID
EZH-108
Other IDs
2020-002669-33
Status last verified
Feb 2025
First submitted
29 Jul 2020
Last updated
19 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tazemetostat, Itraconazole and Rifampin in people with All Malignancies and Advanced Malignancies, run by Epizyme, Inc. at 10 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours of Quantifiable Concentration (AUC0-12h) of Tazemetostat (time frame: Pre-dose (0 hour), 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 15). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04537715.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.

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