Clinical Trial: A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma
Brief 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 tumors:
- Atypical teratoid rhabdoid tumor (ATRT)
- Malignant rhabdoid tumor (MRT)
- Rhabdoid tumor of kidney (RTK)
- Selected tumors with rhabdoid features
- INI1-negative tumors:
- Epithelioid sarcoma
- Epithelioid malignant peripheral nerve sheath tumor
- Extraskeletal myxoid chondrosarcoma
- Myoepithelial carcinoma
- Renal medullary carcinoma
- Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) (with Sponsor approval)
- Synovial Sarcoma with a SS18-SSX rearrangement
Dose Expansion at the MTD or the RP2D, for subjects with rhabdoid tumors (MRT/ATRT/RTK/selected tumors with rhabdoid features).
Detailed Summary:
Sponsor: Epizyme, Inc.
Current Primary Outcome:
- To determine the MTD or the RP2D (Dose Escalation) [ Time Frame: 1 cycle/28 days ]The incidence and severity of treatment-emergent adverse events (AEs) qualifying as protocol-defined DLTs in Cycle 1 will guide establishment of the protocol defined RP2D and/or MTD
- Dose expansion: Number of subjects with objective response using disease appropriate standardized response criteria [ Time Frame: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Dose escalation: Number of subjects with objective response using disease appropriate standardized response criteria [ Time Frame: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months ]
- Dose Expansion: Progression-free survival (PFS) [ Time Frame: At 24 and 56 weeks post treatment using Kaplan-Meier method ]
- Dose Expansion: Overall Survival (OS) [ Time Frame: At 24 and 56 weeks post treatment using Kaplan-Meier method ]
- 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 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax [ Time Frame: Days 1 and 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax [ Time Frame: Days 1 and 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t) [ Time Frame: Days 1 and 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-12) [ Time Frame: Days 1 and 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2 [ Time Frame: Days 1 and 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): CL/F [ Time Frame: Day 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Vd/F [ Time Frame: Day 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ka [ Time Frame: Day 15 ]
- Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ctrough [ Time Frame: Day 1 of cycles 2, 3 and 4 ]
Original Secondary Outcome: Same as current
Information By: Epizyme, Inc.
Dates:
Date Received: October 21, 2015
Date Started: December 2015
Date Completion: January 2018
Last Updated: April 12, 2017
Last Verified: April 2017