A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumours or Synovial Sarcoma

Official Title

A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumours or Synovial Sarcoma

Summary:

This is a Phase I, open-label, dose escalation and dose expansion study with a BID oral dose of 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. The study has two parts: Dose Escalation and Dose Expansion. Dose escalation for subjects with the following relapsed/refractory malignancies: - Rhabdoid tumours: - Atypical teratoid rhabdoid tumour (ATRT) - Malignant rhabdoid tumour (MRT) - Rhabdoid tumour of kidney (RTK) - Selected tumours with rhabdoid features - INI1-negative tumours: - Epithelioid sarcoma - Epithelioid malignant peripheral nerve sheath tumour - Extraskeletal myxoid chondrosarcoma - Myoepithelial carcinoma - Renal medullary carcinoma - Other INI1-negative malignant tumours (e.g., dedifferentiated chordoma) (with Sponsor approval) - Synovial Sarcoma with a SS18-SSX rearrangement Dose Expansion at the MTD or the RP2D - Cohort 1 -(closed to enrollment) ATRT - Cohort 2 - MRT/RTK/selected tumours with rhabdoid features - Cohort 3 - INI-negative tumours: - Epithelioid sarcoma - Epithelioid malignant peripheral nerve sheath tumour - Extraskeletal myxoid chondrosarcoma - Myoepithelial carcinoma - Renal medullary carcinoma - Chordoma (poorly differentiated or de-differentiated) - Other INI1-negative malignant tumours (e.g., dedifferentiated chordoma) with Sponsor approval - Cohort 4 -(closed to enrollment) Tumour types eligible for Cohorts 1 through 3 or synovial sarcoma with SS18-SSX rearrangement

Trial Description

Primary Outcome:

  • To determine the MTD or the RP2D (Dose Escalation)
  • Dose expansion: Number of subjects with objective response using disease appropriate standardized response criteria
Secondary Outcome:
  • Dose escalation: Number of subjects with objective response using disease appropriate standardized response criteria
  • Dose Expansion: Progression-free survival (PFS)
  • Dose Expansion: Overall Survival (OS)
  • Incidence of treatment-emergent adverse events as a measure of safety and tolerability
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t)
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-12)
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): CL/F
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Vd/F
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ka
  • Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ctrough

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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