Clinical Trials /

Tazemetostat in Malignant Peripheral Nerve Sheath Tumors

NCT04917042

Description:

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.

Related Conditions:
  • Malignant Peripheral Nerve Sheath Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tazemetostat in Malignant Peripheral Nerve Sheath Tumors
  • Official Title: Phase 2 Study Using Tazemetostat in Patients With Recurrent/Refractory and/or Metastatic Malignant Peripheral Nerve Sheath Tumors (MPNST)

Clinical Trial IDs

  • ORG STUDY ID: UF-SC-001
  • SECONDARY ID: IRB202100865
  • NCT ID: NCT04917042

Conditions

  • Peripheral Nerve Sheath Tumor

Interventions

DrugSynonymsArms
TazemetostatTAZVERIKtazemetostat

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
tazemetostatExperimental
  • Tazemetostat

Eligibility Criteria

        Inclusion Criteria:

          -  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 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).

               -  XRT/External Beam Irradiation including Protons: > 14 days after local XRT; > 150
                  days after TBI, craniospinal XRT or if radiation to > 50% of the pelvis; > 42
                  days if other substantial BM 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:

               -  Peripheral absolute neutrophil count (ANC) > 1000/mm3.

               -  Platelet count > 100,000/mm2 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 7 days prior to enrollment).

               -  Hemoglobin > 8.0 g/dL at baseline (may receive RBC transfusions).

               -  Creatinine clearance or radioisotope GFR > 70 ml/min/1.73 m2, or serum creatinine
                  based on age/gender

               -  Total bilirubin < 1.5 ULN or direct bilirubin < 1 x ULN.

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN;
                  if liver metastases present, then AST and ALT must be < 5 x ULN.

               -  Serum albumin > 2 g/dL.

               -  Coagulation INR < 1.5, while on anti-coagulation INR < 2.5.

          -  Nervous system disorders (CTCAE v5.0) resulting from prior therapy must be < Grade 2,
             with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible.

          -  Subjects must not have more than one active malignancy at the time of enrollment

          -  Presence of radiographically measurable disease per RECIST 1.1 criteria.

          -  Written informed consent obtained from the subject and the subject agrees to comply
             with all the study-related procedures. All subjects and/or their parents or legally
             authorized representatives must sign a written informed consent. Assent, when
             appropriate, will be obtained according to institutional standard practice.

          -  Use of contraception:

               -  Women of childbearing potential (WOCBP) who are heterosexually active must be
                  using two highly effective methods of contraception to avoid pregnancy throughout
                  the study and for at least 30 days after the last dose of study drug to minimize
                  the risk of pregnancy.

               -  Males with female partners of child-bearing potential must agree to use
                  physician-approved contraceptive methods (e.g., abstinence, condoms,vasectomy)
                  throughout the study and should avoid donating sperm, for 90 days following the
                  last dose of study drug.

        Exclusion Criteria:

          -  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.

          -  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 or myelodysplastic syndrome (MDS).

          -  Subjects who have any of the following underlying major cardiac issues or conditions:

               -  Known QTc prolongation or documentation on screening ECG (QTcF interval on
                  screening ECG ≥ 480 milliseconds).

               -  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.

          -  Females who are pregnant or breastfeeding

          -  Administration of a vaccine containing live virus within 30 days prior to the first
             dose of trial treatment.

          -  Prisoners or subjects who are involuntarily incarcerated, or subjects who are
             compulsorily detained for treatment of either a psychiatric or physical illness.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Progression free survival
Time Frame:3 years
Safety Issue:
Description:Determine the progression free survival, defined as the length of time from the start of treatment to time of progression or death, whichever occurs first.
Measure:Time to progression
Time Frame:2 years
Safety Issue:
Description:Determine the time to progression, defined as the length of time from the start of treatment until disease progression by RECIST 1.1 criteria.
Measure:Clinical benefit
Time Frame:2 years
Safety Issue:
Description:Determine the clinical benefit using the Numbered Pain Rating Scale. A person rates their pain on a scale of 0 to 10 or 0 to 5. Zero means "no pain," and 5 or 10 means "the worst possible pain." These pain intensity levels may be assessed upon initial treatment, or periodically after treatment.
Measure:Clinical benefit rate
Time Frame:2 years
Safety Issue:
Description:Assess the clinical benefit rate, defined as the proportion of subjects with complete or partial response or stable disease (by RECIST 1.1 criteria) lasting at least 4 months.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Florida

Trial Keywords

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

Last Updated

June 28, 2021