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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 ---