Tazemetostat in Malignant Peripheral Nerve Sheath Tumors

NCT04917042 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: UF-SC-001IRB202100865OCR40197
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2, open label, single arm study will investigate the use of tazemetostat in patients with recurrent/refractory and/or metastatic malignant peripheral nerve sheath tumors.

Conditions

Peripheral Nerve Sheath Tumor

Keywords

metastatic malignant peripheral nerve sheath tumors; Enhancer of zeste homolog 2 (EZH2) inhibition; sarcoma; pediatric; tazemetostat

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Assess the objective response rate, defined as the proportion of subjects who achieve either a complete response or partial response based on radiographic evaluation of treatment response via RECIST1.1. A complete response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. A partial response is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.

  143 days

Secondary Outcomes (4)

• Progression Free Survival

  143 days

• Time to Progression

  143 days

• Clinical Benefit

  143 days

• Clinical Benefit Rate

  143 days

Study Arms (1)

tazemetostat

EXPERIMENTAL

Drug: Tazemetostat

Interventions

Tazemetostat DRUG

Subjects will receive 520 mg/m2/dose (subjects 12-17 years old) or 800 mg of tazemetostat orally twice daily in 28 day cycles. Subjects will receive treatment with tazemetostat up to 2 years or until disease progression or unacceptable toxicity occurs.

Also known as: TAZVERIK

tazemetostat

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A histologic confirmation of recurrent/refractory and/or metastatic malignant peripheral nerve sheath tumor with Response Evaluation Criteria in Solid Tumors (RECIST) measurable disease
• Patients ≥ 12 years of age at the time of enrollment
• Performance status: 12-15 years old: Lansky \> 50; 16-17 years old: Karnofsky \> 50; ≥ 18 years old: Eastern Cooperative Group (ECOG) score 0-2
• Subjects must have adequately recovered from the acute toxic effects of all prior anti-cancer therapy per enrolling physician and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
• Anti-cancer agents known to be Myelosuppressive: ≥ 28 days after the last dose of agent.
• Anti-cancer agents not known to be myelosuppressive: \> 7 days after the last dose of agent.
• Antibodies: \> 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade \< 1.
• Systemic Corticosteroids: if related to prior therapy \> 14 days must have elapsed, or on stable dose for treatment of CNS disease.
• Hematopoietic growth factors: \> 14 days after the last dose of a long-acting growth factor.
• Interleukins, Interferons, and Cytokines (other than hematopoietic growth factors): \> 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
• Radiation therapy (XRT)/External Beam Irradiation including Protons: \> 14 days after local XRT; \> 150 days after traumatic brain injury, craniospinal XRT or if radiation to \> 50% of the pelvis; \> 42 days if other substantial bone marow radiation.
• Radiopharmaceutical therapy: \> 42 days after systemically administered radiopharmaceutical therapy.
• Major surgery \> 14 days prior, with evidence of wound healing and no active surgical complications
• Subjects must not have had prior exposure to Tazemetostat or other inhibitor(s) of EZH2
• Adequate laboratory values of organ function, defined as:

You may not qualify if:

• Subjects who are currently taking the following concomitant medications:
• Anti-cancer Agents: Subjects who are currently receiving other anti-cancer agents are not eligible.
• CYP3A4 Agents: Subjects who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 are prohibited from 14 days prior to the first dose of Tazemetostat to the end of the study. Note: Dexamethasone for CNS tumors or metastases, on a stable dose, is allowed.
• Grapefruit, grapefruit juice, Seville oranges and food/drinks containing them should be avoided one week before the first dose of the study intervention
• Subjects who are acutely ill with an uncontrolled active infection on systemic anti-infective agents are not eligible.
• Subjects with a prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL) or other myeloproliferative neoplasm (MPN).
• Subjects who have any of the following underlying major cardiac issues or conditions:
• Known QTc prolongation or documentation
• Documented New York Heart Association (NYHA) Class III or IV congestive heart failure.
• Myocardial infarction within 6 months prior to registration.
• Unstable angina within 6 months prior to registration.
• Symptomatic arrhythmia.
• Subjects who in the opinion of the investigator may be high risk for treatment complications or unable to comply with the safety monitoring requirements of the study
• Heterosexually active males or females of reproductive potential may not participate unless they have agreed to use two highly effective contraceptive methods for the duration of study treatment as Tazemetostat might counteract the effects of hormonal contraceptives. Female subjects of childbearing potential should agree to remain abstinent or use adequate contraceptive methods for 6 months after the last dose of Tazemetostat. Male subjects should agree to remain abstinent or use adequate contraceptive methods, and agree to refrain from donating sperm, and for 90 days after the last dose of Tazemetostat.
• Females who are pregnant or breastfeeding will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.

Sponsors & Collaborators

• University of Florida: lead
• Epizyme, Inc.: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Nerve Sheath Neoplasms; Neurofibrosarcoma; Inhibition, Psychological; Sarcoma

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neurofibroma; Behavior

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Joanne Lagmay, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 8, 2021
• Study Start: August 25, 2021
• Primary Completion: February 14, 2025
• Study Completion: April 1, 2026
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2026-02

Locations

US (1)