This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Study of the EZH2 Inhibitor Tazemetostat in Malignant Mesothelioma

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Epizyme, Inc.
Sponsor:
Information provided by (Responsible Party):
Epizyme, Inc.
ClinicalTrials.gov Identifier:
NCT02860286
First received: July 27, 2016
Last updated: March 23, 2017
Last verified: March 2017
  Purpose

This is a Phase 2, multicenter, open-label, 2-part, single-arm, 2-stage study of tazemetostat 800 mg two times a day (BID) administered orally. Screening of subjects to determine eligibility for the study will be performed within 21 days of the first planned dose of tazemetostat.

In Part 1, 12 subjects with relapsed or refractory malignant mesothelioma regardless of BAP1 status will be treated and undergo pharmacokinetics (PK) blood sample collection after a single tazemetostat 800 mg.

Part 2 will include subjects with BAP1-deficient relapsed or refractory malignant mesothelioma.

Treatment with tazemetostat will continue until disease progression, unacceptable toxicity or withdrawal of consent, or termination of the study. Response assessment will be evaluated after 6 weeks of treatment and then every 12 weeks thereafter while on study.


Condition Intervention Phase
Mesothelioma BAP1 Loss of Function Drug: Tazemetostat Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects With Relapsed or Refractory Malignant Mesothelioma With BAP1 Loss of Function

Resource links provided by NLM:


Further study details as provided by Epizyme, Inc.:

Primary Outcome Measures:
  • Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax [ Time Frame: Days 1 and 15 ]
  • Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax [ Time Frame: Days 1 and 15 ]
  • Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t) [ Time Frame: Days 1 and 15 ]
  • Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-∞) [ Time Frame: Days 1 and 15 ]
  • Part 1: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2 [ Time Frame: Days 1 and 15 ]
  • Part 1: Incidence of treatment-emergent adverse events as a measure of safety and tolerability [ Time Frame: Adverse events assessed from first dose through 30 days post last dose ]
  • Part 2: To assess disease control rate (DCR) defined as number of subjects with complete response (CR), partial response (PR) and stable disease (SD) [ Time Frame: 12 weeks ]

Secondary Outcome Measures:
  • Part 1 and 2: Incidence of treatment-emergent adverse events as a measure of safety and tolerability [ Time Frame: Adverse events assessed from first dose through 30 days post last dose ]
  • Part 1 and 2: Overall response rate (ORR; complete response + partial response [CR + PR]) [ Time Frame: Assessed every 6 weeks for duration of study participation which is estimated to be 12 months ]
  • Part 1 and 2: Progression-free survival (PFS) [ Time Frame: 12 weeks and 24 weeks as the time from the date of the first dose of study treatment to the date of death due to any cause ]
  • Part 1 and 2: Overall survival (OS) [ Time Frame: 12 weeks and 24 weeks as the time from the date of the first dose of study treatment to the date of death due to any cause assessed for up to 24 months ]
  • Part 1 and 2: To evaluate the duration of response (DOR) in subjects with confirmed CR or PR [ Time Frame: Every 6 weeks up to disease progression or start of new anti-cancer therapy assessed for up to 12 months ]
  • Part 1: Disease Control Rate (DCR) [ Time Frame: 12 weeks ]
  • Part 2: Population PK parameters: Cmax [ Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days ]
  • Part 2: Population PK parameters: Tmax [ Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days ]
  • Part 2: Population PK parameters: AUC(0-t) [ Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days ]
  • Part 2: Population PK parameters: AUC(0-∞) [ Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days ]
  • Part 2: Population PK parameters: t1/2 [ Time Frame: Days 1 and 15 of Cycle 1, and Days 1 of Cycles 2 through 4, where each cycle is 21 days ]
  • Part 2: Changes in H3K27me3 levels in tumor tissue as assessed by IHC [ Time Frame: 6 or 12 weeks ]

Estimated Enrollment: 67
Study Start Date: July 2016
Estimated Study Completion Date: November 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-Label Tazemetostat
Oral Tazemetostat 800mg BID
Drug: Tazemetostat
Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene.
Other Names:
  • EPZ-6438
  • E7438

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age (at the time of consent) ≥18 years of age
  2. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  3. Has a life expectancy of >3 months
  4. Has mesothelioma (pleural, peritoneal, pericardial, tunica vaginalis) of any histology that is relapsed or refractory after treatment with at least one pemetrexed-containing regimen
  5. Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) or equivalent laboratory certification
  6. Part 2: Molecular evidence of BAP1 loss of function mutation present on local pathology, e.g., lack of nuclear BAP1 staining by immunohistochemistry (IHC) or evidence of loss of function by gene sequencing
  7. Has sufficient archival tumor tissue (a minimum of 10 slides or tumor block) available for central retrospective testing of BAP1 status
  8. 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 and not clinically significant, at time of enrollment
  9. Prior therapy(ies), if applicable, must be completed according to the criteria below prior to first dose of tazemetostat:

    • Cytotoxic chemotherapy; at least 21 days since last dose
    • Non-cytotoxic chemotherapy (e.g., small molecule inhibitor); at least 14 days since last dose
    • Monoclonal antibody; at least three half-lives since the last dose
    • Non-antibody immunotherapy (e.g., tumor vaccine); at least 42 days since last dose
    • Radiotherapy, at least 14 days from last local site radiotherapy
    • Hematopoietic growth factor; at least 14 days from last dose
    • Investigational drug; 30 days or five half-lives, whichever is longer, from last dose
  10. Has measurable disease based on either modified RECIST [Nowak 2005] for thoracic disease or RECIST 1.1 elsewhere
  11. Has adequate hematologic (bone marrow and coagulation factors), renal, and hepatic function as defined by criteria below:

    • Hemoglobin ≥9 mg/dL
    • Platelets ≥100,000/mm3 (≥100 × 109/L) without platelet transfusion for 7 days
    • ANC ≥1000/mm3 (≥1.0 × 109/L) without growth factor support for 14 days
    • Coagulation: Prothrombin time (PT) <1.5 × ULN and partial thromboplastin time (PTT) <1.5 × ULN
    • Creatinine < 2.0 × ULN
    • Hepatic function: Conjugated bilirubin <1.5 × ULN and ALT and AST <3 × ULN
  12. Has a QT interval corrected by Fridericia's formula (QTcF) ≤480 msec
  13. Willing to provide tissue for translational research
  14. Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required and subject also should agree to use an adequate method of contraception starting with screening through 30 days after the last dose of study therapy (if sexually active).
  15. Male subjects should agree to use condoms starting with the first dose of study therapy through 30 days after the last dose of study therapy if sexually active with a female of childbearing potential

Exclusion Criteria:

  1. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
  2. Has a history of known central nervous system metastasis
  3. Has had a prior malignancy other than the malignancies under study Exception: A subject who has been disease-free for 5 years, or a subject with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma is eligible.
  4. Has had major surgery within 3 weeks prior to enrollment (a percutaneous biopsy, pleural catheter insertion, placement of central venous catheter or other minor procedure are permitted)
  5. Is unwilling to exclude grapefruit juice, Seville oranges and grapefruit from the diet and all foods that contain those fruits from time of enrollment throughout their time on study
  6. 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
  7. Is currently taking any prohibited medication(s)
  8. Has an active infection requiring systemic treatment
  9. Has a congenital or acquired immunodeficiency, including subjects with known history of infection with human immunodeficiency virus (HIV) NOTE: HIV-positive subjects who are taking antiretroviral therapy are ineligible due to potential PK interactions with tazemetostat.
  10. Has known history of chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (detectable anti-hepatitis C circulating viral RNA)
  11. Has had a deep venous thrombosis (DVT) or pulmonary embolism within the 3 months prior to study enrollment.

    NOTE: Subjects with a history of a DVT or pulmonary embolism >3 months prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study.

  12. Is pregnant or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02860286

Contacts
Contact: Maria Roche, NP 855-500-1011 clinicaltrials@epizyme.com
Contact: Peter Ho, PhD 855-500-1011 clinicaltrials@epizyme.com

Locations
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90025
Contact: Lien Hua-Feng       Lhua@mednet.ucla.edu   
Principal Investigator: Robert Cameron, MD         
City of Hope National Medical Center Recruiting
Los Angeles, California, United States, 90301
Contact: Allana Glines-Bull       aglines@coh.org   
Principal Investigator: Marianna Koczywas, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Principal Investigator: Thierry Jahan, MD         
United States, Maryland
University of Maryland Medical Center Not yet recruiting
Baltimore, Maryland, United States, 21201
Contact: Maha Khalil       mkhalil@umm.edu   
Principal Investigator: Petr Hausner, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Alexandra Wanat         
Principal Investigator: Christopher Azzoli, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Bronwyn Wada-Gill       bronwynm_wada-gill@dfci.harvard.edu   
Principal Investigator: David Jackman, MD         
United States, Minnesota
Mayo Clinic - Rochester Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Tobias Peikert, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sharon Amir       amirs@mskcc.org   
Contact: Edward McDonnell       mcdonnee@mskcc.org   
Principal Investigator: Marjorie Zauderer, MD         
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Principal Investigator: Anne Tsao, MD         
France
Institut Bergonie Recruiting
Bordeaux Cedex, France, 33076
Contact: Mitchelle Rinaldo       M.Rinaldo@bordeaux.unicancer.fr   
Principal Investigator: Sylvestre Le Moulec, MD         
CHRU de Lille Recruiting
Lille, France, 59037
Contact: Marianne Gierczynski       marianne.gierczynksi@chru-lille.fr   
Principal Investigator: Arnaud Scherpereel, MD         
Institut Gustave Roussy Recruiting
Villejuif cedex, France, 94805
Contact: Kevinee Khoobarry       kevinee.khoobarry@gustaveroussy.fr   
Principal Investigator: David Planchard, MD         
United Kingdom
University Hospital of South Manchester Recruiting
Greater Manchester, United Kingdom, M23 9LT
Contact: Zahra Zahid       zahra.zahid@uhsm.nhs.uk   
Principal Investigator: Paul Taylor, MD         
University of Leicester & Leicester University Hospitals Recruiting
Leicester, United Kingdom, LE1 9HN
Contact: Nicole Clamp       nicole.clamp@uhl-tr.nhs.uk   
Principal Investigator: Dean Fennel, MD         
St. Bartholomew's Hospital Recruiting
London, United Kingdom, EC1M 6BQ
Contact: Marina Baccarini       marina.baccarini@bartshealth.nhs.uk   
Principal Investigator: Peter Szlosarek, MD         
University College Hospital Recruiting
London, United Kingdom, NW1 2PG
Contact: Pavlos Zinzalias       Pavlos.Zinzalias@uclh.nhs.uk   
Principal Investigator: Martin Forster, MD         
Royal Marsden Hospital - Chelsea Recruiting
London, United Kingdom, SW3 6JJ
Contact: Sarah Vaughan       sarah.vaughan@rmh.nhs.uk   
Principal Investigator: Sanjay Popat, MD         
Royal Marsden Hospital - Surrey Recruiting
Surrey, United Kingdom, SM2 5PT
Contact: Kathryn Priest       Kathryn.priest@rmh.nhs.uk   
Principal Investigator: Sanjay Popat, MD         
Sponsors and Collaborators
Epizyme, Inc.
  More Information

Responsible Party: Epizyme, Inc.
ClinicalTrials.gov Identifier: NCT02860286     History of Changes
Other Study ID Numbers: EZH-203
Study First Received: July 27, 2016
Last Updated: March 23, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
Mesothelioma
Lung Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 24, 2017