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Diffuse Large B Cell LymphomaPhase 1NCT03010982

Open-Label, Multi-Center, Two-Part, Ph1 Study to Characterize the PKs of an Intravenous Micro-Dose of [14C]-Tazemetostat (EPZ 6438) and the ADME of an Oral [14C]-Labeled Dose of Tazemetostat in Subjects With B-Cell Lymphomas or Adv Solid Tumors

A Phase 1 study testing Tazemetostat and [14C] Tazemetostat in people with Diffuse Large B Cell Lymphoma and Primary Mediastinal Lymphoma, run by Epizyme, Inc. at 2 sites in United Kingdom.

Completed

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

Official record
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Trial summary

This is a Phase 1, open-label, two-part study designed to characterize the PK of an IV dose of approximately 12 µg tazemetostat that contains approximately 500 nCi of [14C] tazemetostat and the ADME of an oral dose of 800 mg tazemetostat that contains approximately 400 µCi of [14C]-labeled tazemetostat in three… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tazemetostat and [14C] Tazemetostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesUnited Kingdom
Study dates
20 Jun 2018to 8 Jan 2019
Phase
Phase 1
Are there results?
None posted in the registry

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 ≥ 18 years of age at time of consent
  • Female ≥ 18 years of age at time of consent and of non-childbearing potential. A woman is considered to be of non-childbearing potential if she has reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause) or has undergone surgical sterilization (removal of ovaries and/or uterus). Note: Postmenopausal state will be confirmed with FSH test completed during the screening period.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Has a life expectancy of >3 months
  • Has EITHER histologically confirmed B-cell lymphomas including but not limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal B-cell lymphoma (PMBCL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or Hodgkin lymphoma (HL) and has relapsed or refractory disease following at least two lines of prior standard therapy, including alkylator/anthracycline (unless anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy (R-CHOP, rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone or dexamethasone, or equivalent for non-Hodgkin lymphoma), AND must be considered unable to benefit from intensification treatment with autologous hematopoietic stem cell transplantation (ASCT) , as defined by meeting at least one of the following criteria:
  • Relapsed following, or refractory to, previous ASCT
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  • Did not achieve at least a partial response to a standard salvage regimen (e.g., R-ICE, rituximab, ifosfamide, carboplatin, etoposide, or R-DHAP, rituximab, dexamethasone, cytarabine, cisplatin)
  • Ineligible for intensification treatment due to age or significant comorbidity
  • Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
  • Refused intensification treatment and/or ASCT
  • OR
  • Histologically and/or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with approved therapies or for which there are no standard therapies available
  • May have evaluable or measurable disease
  • Has all prior treatment (i.e., chemotherapy, immunotherapy, radiotherapy) related clinically significant toxicities resolve to ≤ Grade 1 per CTCAE, version 4.03 or are clinically stable, at time of consent
  • Time between the last dose of the latest therapy and the first dose of study drug:
  • Chemotherapy: cytotoxic - at least 21 days
  • Chemotherapy: nitrosureas - at least 6 weeks
  • Chemotherapy: non-cytotoxic (e.g. small molecule inhibitor) - at least 14 days
  • Monoclonal antibody (ies) - at least 28 days
  • Immunotherapy (e.g. tumor vaccine) - at least 28 days
  • Radiotherapy (RT) - at least 21 days for stereotactic radiosurgery, at least 12 weeks for craniospinal, ≥50% radiation of pelvis, or total body irradiation
  • High dose therapy with autologous hematopoietic cell infusion - at least 60 days
  • Hematopoietic growth factor - at least 14 days
  • Has adequate hematologic (bone marrow [BM] and coagulation factors), renal and hepatic function as defined by criteria below:
  • Hemoglobin ≥9 g/dL
  • Platelet ≥75,000/mm3 (≥75 × 10^9/L)
  • ANC ≥750/mm3 (≥0.75 × 10^9/L)
  • PT< 1.5 ULN
  • PTT< 1.5 ULN
  • Creatinine < 2.0 ULN
  • Conjugated bilirubin < 1.5 × ULN
  • AST <3 × ULN I. ALT <3 × ULN NOTE: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may retest the subject and the subsequent within range screening result may be used to determine the subject's eligibility
  • Subjects with a history of Hepatitis B or C are eligible on the condition that subjects have adequate liver function as defined the protocol and are hepatitis B surface antigen negative and/or have undectable HCV RNA.
  • Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec
  • Subject must have regular bowel movements (minimum of 1 bowel movement every day or every other day; no more than 3 bowel movements per day) for the past 2 weeks without diarrhea (>4 bowel movements per day) or constipation (fewer than 3 bowel movements in 1 week). No known medical history of a disease or syndrome that affects bowel function (e.g., irritable bowel syndrome, inflammatory bowel disease, ulcerative colitis, etc.), fecal incontinence, and no history of significant opioid induced constipation within the past 3 months
  • Subject must have the ability to regularly void urine with no current evidence of urinary incontinence, urinary retention, uncorrected congenital defects that interfere with normal urinary system function, chronic urinary tract infections, or other conditions that may interfere with normal urinary bladder emptying. In the past 3 months, no obstructive uropathy, surgery affecting urinary system (e.g., radical prostatectomy, TURP, etc.), urinary tract infection. Subjects with solitary kidney are excluded from the study
  • Male subjects must refrain from donating sperm starting at the planned first dose of study drug until 30 days following the last dose of study drug. Male subjects with a female partner of childbearing potential must be vasectomized, or remain abstinent or use a condom as defined in Section 8.3.8, starting at the planned first dose of study drug until 30 days following the last dose of study drug. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Female partners of male subjects who are of childbearing potential must also adhere to one of the following:
  • Placement of an intrauterine device or intrauterine system.
  • Established use of oral, injected or implanted hormonal methods of contraception.
  • Progesterone only oral contraception, where inhibition of ovulation is not the primary mode of action.

Who cannot join

  • Subjects meeting ANY of the following criteria must NOT be enrolled in this study:
  • Has participated in a study in which [14C] was administered within the last 6 months prior to screening for this study
  • Has CNS or leptomeningeal metastasis
  • Has had a prior malignancy other than the malignancies under study Exception: Subject who has been disease-free for 3 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
  • Has had major surgery within 3 weeks prior to enrollment NOTE: Minor surgery (e.g., minor biopsy, central venous catheter placement) is permitted within 3 weeks prior to enrollment
  • Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment to while on study
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  • Has cardiovascular impairment, history of congestive heart failure greater than NYHA Class II uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months prior to the planned first dose of tazemetostat; or ventricular cardiac arrhythmia requiring medical treatment
  • Subjects taking medications that are known potent CYP3A4 inducers/inhibitors (including St. John's Wort) from 14 days prior to the first dose of study medications (see http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm080499.htm; or http://medicine.iupui.edu/clinpharm/ddis/ for a list of potent CYP3A4 inducers and inhibitors).
  • Has an active infection requiring systemic treatment
  • Is immunocompromised, including subjects with known history of infection with human immunodeficiency virus (HIV)
  • Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable HCV RNA)
  • Has had a venous thrombosis or pulmonary embolism within the 3 months prior to study enrollment.
  • NOTE: Subjects with a history of a deep vein thrombosis >3 months prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study.
  • Has known hypersensitivity to any of the components of study drug
  • Is unable to take oral medications, malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea or vomiting) that might impair the bioavailability of study drug
  • Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Is unwilling to adhere to contraception criteria from time of enrollment in study to at least 30 days after last dose of study drug
  • Clinical history, current alcohol (ethanol), or illicit drug use which, in the judgment of the investigator, will interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations
  • A history of bleeding (i.e., hemoptysis, hematuria, GI blood loss, epistaxis, or others with greater than Grade 1 according to National Cancer Institute Common Terminology Criteria Version 4.0 [NCI-CTC v4.0]) within 1 month prior to beginning therapy or any clinical indications of current active bleeding

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Bebington, Wirral

  • Royal Liverpool and Broadgreen University Hospital Trust

    Liverpool, L7 8XP

Other trials in United Kingdom

About this study

Official title: An Open-Label, Multi-Center, Two-Part, Phase 1 Study to Characterize the Pharmacokinetics of an Intravenous Micro-Dose of [14C]-Tazemetostat (EPZ 6438) and the Absorption, Distribution, Metabolism and Elimination of an Oral [14C]-Labeled Dose of Tazemetostat in Subjects With B-Cell Lymphomas or Advanced Solid Tumors

This is a Phase 1, open-label, two-part study designed to characterize the PK of an IV dose of approximately 12 µg tazemetostat that contains approximately 500 nCi of [14C] tazemetostat and the ADME of an oral dose of 800 mg tazemetostat that contains approximately 400 µCi of [14C]-labeled tazemetostat in three subjects with B-cell lymphomas or advanced solid tumors.

Being tested
Tazemetostat and [14C] Tazemetostat
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • Tazemetostat and [14C] TazemetostatDrug

    Also called E7438, EPZ-6438

    Tazemetostat is a selective oral small molecule inhibitor of EZH2.

Study groups in NCT03010982
Study groupRoleWhat they receive
Tazemetostat and [14C] TazemetostatExperimental* Tazemetostat 800 mg BID orally as tablets continuously starting on Day 1, with the exception of the morning dose on Day 16; * A single IV dose of approximately 12 µg tazemetostat that contains approximately 500 nCi of [14C] tazemetostat on Day 15; * A single oral dose of 800 mg tazemetostat as a solution containing approximately 400 µCi (14.8 MBq) of [14C] tazemetostat on Day 16.
Receives: Drug: Tazemetostat and [14C] Tazemetostat

What is being measured

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

  1. Plasma PK of [14C] tazemetostat, tazemetostat, and its metabolite EPZ-6930 after IV administration of approximately 12 µg of [14C] tazemetostat containing approximately 500 nCi of radioactivity and oral BID administration of 800 mg tazemetostat (AUC 0-7)

    Measured: Day 15

  2. Total recovery and relative excretion of radioactivity in urine and feces after an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity

    Measured: Day 16

Secondary outcomes (7)

  1. Estimate tazemetostat absolute bioavailability (F) after repeated oral administration of 800 mg BID (AUC 0-12 and AUC 0-~)

    Measured: Day 15

  2. Compare the total radioactivity concentration-time profiles in blood and plasma after oral administration of [14C] tazemetostat (AUC 0-t, AUC 0-12, AUC 0-~)

    Measured: Day 16

  3. Determine peak plasma concentration (Cmax) after oral administration of [14C] tazemetostat

    Measured: Day 16

  4. Determine the plasma terminal half-life (t1/2) after oral administration of [14C] tazemetostat

    Measured: Day 16

  5. Plasma PK of tazemetostat and EPZ6930 after administration of an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity (Plasma AUC 0-t, AUC 0-12)

    Measured: Day 16

  6. Determine the peak plasma concentration (Cmax) of tazemetostat and EPZ6930 after administration of an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity

    Measured: Day 16

  7. Determine the time to peak plasma concentration (Tmax) tazemetostat and EPZ6930 after administration of an oral 800 mg dose of [14C] tazemetostat containing approximately 400 µCi (14.8 MBq) of radioactivity

    Measured: Day 16

Timeline

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

  1. First posted5 Jan 2017 (estimated)
  2. Study start20 Jun 2018
  3. Primary completion8 Jan 2019
  4. Study completion8 Jan 2019

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03010982
Sponsor's protocol ID
EZH-103
Other IDs
2016-002166-32, 2016
Status last verified
Mar 2024
First submitted
19 Dec 2016
Last updated
22 Mar 2024
Results posted
No
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 and [14C] Tazemetostat in people with Diffuse Large B Cell Lymphoma and Primary Mediastinal Lymphoma, run by Epizyme, Inc. at 2 sites in United Kingdom.

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 40 inclusion and 19 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 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Plasma PK of [14C] tazemetostat, tazemetostat, and its metabolite EPZ-6930 after IV administration of approximately 12 µg of [14C] tazemetostat containing approximately 500 nCi of radioactivity and oral BID administration of 800 mg tazemetostat (AUC 0-7) (time frame: Day 15). The study lists 2 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 NCT03010982.

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 22 Mar 2024.

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