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Report for Clinical Trial NCT02601937
 Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene 
      This is a Phase I, open-label, dose escalation and dose expansion study with BID (suspension)
      and TID (tablet) 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
        -  Cohort 1 -(closed to enrollment) ATRT
        -  Cohort 2 - MRT/RTK/selected tumors with rhabdoid features
        -  Cohort 3 - INI-negative tumors:
             -  Epithelioid sarcoma
             -  Epithelioid malignant peripheral nerve sheath tumor
             -  Extraskeletal myxoid chondrosarcoma
             -  Myoepithelial carcinoma
             -  Renal medullary carcinoma
             -  Chordoma (poorly differentiated or de-differentiated)
             -  Other INI1-negative malignant tumors (e.g., dedifferentiated chordoma) with Sponsor
                approval
        -  Cohort 4 -(closed to enrollment) Tumor types eligible for Cohorts 1 through 3 or
           synovial sarcoma with SS18-SSX rearrangement
    
Name: Tazemetostat
Description: Tazemetostat (EPZ-6438) is a selective small molecule inhibitor of the histone-lysine methyltransferase EZH2 gene.
 Type: Drug
Group Labels:  1  Open-label Tazemetostat  
  Primary Outcomes 
 Description: 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
 Measure: To determine the MTD or the RP2D (Dose Escalation)
 Time: 1 cycle/28 days
 Measure: Dose expansion: Number of subjects with objective response using disease appropriate standardized response criteria
 Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months
    
Secondary Outcomes 
 Measure: Dose escalation: Number of subjects with objective response using disease appropriate standardized response criteria Time: Assessed every 8 weeks for duration of study participation which is estimated to be 24 months
 Measure: Dose Expansion: Progression-free survival (PFS) Time: At 24 and 56 weeks post treatment using Kaplan-Meier method
 Measure: Dose Expansion: Overall Survival (OS) Time: At 24 and 56 weeks post treatment using Kaplan-Meier method
 Measure: Incidence of treatment-emergent adverse events as a measure of safety and tolerability Time: Adverse events assessed from first dose through 30 days post last dose
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Cmax Time: Days 1 and 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Tmax Time: Days 1 and 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-t) Time: Days 1 and 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): AUC(0-12) Time: Days 1 and 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): t1/2 Time: Days 1 and 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): CL/F Time: Day 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Vd/F Time: Day 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ka Time: Day 15
 Measure: Pharmacokinetics profile of tazemetostat and its metabolite (plasma): Ctrough Time: Day 1 of cycles 2, 3 and 4
 
Purpose: Treatment
Allocation: N/A
Single Group Assignment 
There is one SNP
SNPs
1 V617F 
JAK2 V617F) observed in cytogenetic testing and DNA sequencing. --- V617F ---