EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma

Completed · Phase 1

Conditions studied: Rhabdoid Tumors, INI1-negative Tumors, Synovial Sarcoma, Malignant Rhabdoid Tumor of Ovary

In brief

This is a Phase I, open-label, dose escalation and dose expansion study with BID (suspension) and TID (tablet) oral dose of the enhancer of zeste homolog-2 (EZH2) inhibitor, tazemetostat. Subjects will be screened for eligibility within 14 days of the planned first dose of tazemetostat. A treatment cycle will be 28 days. Response assessment will be evaluated after 8 weeks of treatment and subsequently every 8 weeks while on study.

Key facts

Study ID

NCT02601937

Run by

Epizyme, Inc.

People needed

109

Starts

2016-01-07

Expected to finish

2021-10-22

Last updated by the study team

2024-10-03

Who can join

Age: 1 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age (at the time of consent/assent): ≥6 months to <18 years
• Cohort 4 only: ≥10 years to <18 years
• Performance Status:
• If <12 years of age: Lanksy Performance Status >50%
• If ≥12 years of age: Karnofsky Performance Status >50% NOTE: If subject is unable to walk due to paralysis, but is mobile in a wheelchair, subject is considered to be ambulatory for the purpose of assessing their performance status.
• Has provided signed written informed consent/assent
• Has a life expectancy of >3 months
• Has relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion
• Is ineligible or inappropriate for other treatment regimens known to have effective potential
• 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
• 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
• Has completed a prior therapy (ies) according to the criteria below:
• Other investigational study agent (any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric) (At least 30 days or five half-lives, whichever is longer, since last dose prior to the first dose of tazemetostat)
• Chemotherapy: cytotoxic (At least 14 days since last dose of chemotherapy prior to first dose of tazemetostat)
• Chemotherapy: nitrosoureas (At least 6 weeks since last dose of nitrosoureas prior to first dose of tazemetostat)
• Chemotherapy: non-cytotoxic (e.g., small molecule inhibitor) (At least 14 days since last dose of non-cytotoxic chemotherapy prior to first dose of tazemetostat)
• Monoclonal antibody (ies) (At least 28 days since the last dose of any monoclonal antibody prior to first dose of tazemetostat)
• Immunotherapy (e.g., tumor vaccine) At least 6 weeks since last dose of immunotherapy agent(s) prior to first dose of tazemetostat)
• Radiotherapy (RT) (At least 14 days from last local site RT prior to first dose of tazemetostat/At least 21 days from stereotactic radiosurgery prior to first dose of tazemetostat/At least 12 weeks from craniospinal, ≥ 50% radiation of pelvis, or total body irradiation prior to first dose of tazemetostat)
• Hematopoietic growth factor (At least 14 days from last dose of hematopoietic growth factor prior to first dose of tazemetostat)
• Hematopoietic cell transplantation (At least 60 days from infusion of hematopoietic cells prior to first dose of tazemetostat)
• Has adequate hematologic (bone marrow and coagulation factors), renal and hepatic function as defined by criteria below:
• Hematologic (BM Function):
• Hemoglobin ≥ 8 g/dL
• Platelets ≥100,000/mm\^3 (≥100 x 10\^9/L)

You may not qualify if…

• Has had prior exposure to tazemetostat or other inhibitor(s) of EZH2
• Is being actively treated for another concurrent malignancy or is less than five years from completion of treatment for another malignancy
• Has participated in another interventional clinical study and received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the planned first dose of tazemetostat
• Has had major surgery within 2 weeks prior to enrollment NOTE: Minor surgery (e.g., minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 2 weeks prior to enrollment.
• Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE 4.03 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS). Has abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and MPN (e.g. JAK2 V617F) observed in cytogenetic testing and DNA sequencing.
• Note: Bone marrow aspirate/biopsy will be conducted following abnormal peripheral blood smear morphology assessment conducted by central lab at screening. Cytogenetic testing and DNA sequencing will be conducted following an abnormal result of bone marrow aspirate/biopsy.
• Has a prior history of T-LBL/T-ALL.
• Has clinically active heart disease including prolonged corrected QTcF (>450 msec)
• Is currently taking any prohibited medication(s) as described in Section 7.3.
• 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
• Has an active infection requiring systemic treatment
• Is immunocompromised (i.e. congenital immunodeficiencies), including subjects 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 symptomatic venous thrombosis within the 14 days prior to study enrollment NOTE: Subjects with a history of a deep vein thrombosis 14 days prior to study enrollment who are on anticoagulation therapy with low molecular weight heparin are eligible for this study
• For subjects with CNS involvement (primary tumor or metastatic disease): Have any active bleeding, or new intratumoral hemorrhage of more than punctate size on Screening MRI obtained within 14 days of starting study drug,or known bleeding diathesis or treatment with anti-platelet or anti-thrombotic agents 15.15. Has known hypersensitivity to any of the components of tazemetostat or other inhibitor(s) of EZH2, or hypersensitivity to Ora-sweet or methylparaben
• Has an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements 17. For female subjects of childbearing potential: Is pregnant or nursing For male subjects: Is unwilling to adhere to contraception criteria from time of enrollment in study to at least 30 days after last dose of tazemetostat.

Where it is running

• Children's Hospital of Los Angeles — Los Angeles, California, United States
• University of California San Francisco - Benioff Children's Hospital — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Ann and Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States
• John Hopkins Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Massachusetts General Hospital - Cancer Center — Boston, Massachusetts, United States
• Memorial Sloan Kettering — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Oregon Health & Science University (OHSU) — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• St. Jude Children's Research Hospital, Inc. — Memphis, Tennessee, United States
• UT Southwestern Medical Center — Dallas, Texas, United States
• Texas Children's Cancer and Hematology Center — Houston, Texas, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Sydney Children's Hospital — Sydney, New South Wales, Australia
• Lady Cilento/Queensland Children's Hospital — South Brisbane, Queensland, Australia
• The Royal Children's Hospital — Melbourne, Victoria, Australia
• The Childrens Hospital at Westmead Oncology Unit — Westmead, Australia
• The Hospital for Sick Children — Toronto, Ontario, Canada
• Rigshospitalet Department of Oncology Blegdamsvej — Copenhagen, Denmark
• Institut Curie — Paris, France
• Institut Gustave Roussy — Villejuif, France

Full record on ClinicalTrials.gov

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