Description:
Ewing sarcoma is characterized by genomic rearrangements resulting in over-expression of ets
family transcription factors driving tumor progression. TK216 is designed to inhibit this
effect by inhibiting downstream effects of the EWS-FLI1 transcription factor. This study is a
first in human study of TK216 in subjects with Ewing sarcoma. The study is designed to
establish initial safety and efficacy data in monotherapy and in combination with vincristine
to assess the potential of TK216 for further development.
Title
- Brief Title: TK216 in Patients With Relapsed or Refractory Ewing Sarcoma
- Official Title: A Phase 1 / 2, Dose Escalation Study of Intravenous TK216 in Patients With Relapsed or Refractory Ewing Sarcoma
Clinical Trial IDs
- ORG STUDY ID:
TK216-01
- NCT ID:
NCT02657005
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| TK216 | | TK216 treatment |
Purpose
Ewing sarcoma is characterized by genomic rearrangements resulting in over-expression of ets
family transcription factors driving tumor progression. TK216 is designed to inhibit this
effect by inhibiting downstream effects of the EWS-FLI1 transcription factor. This study is a
first in human study of TK216 in subjects with Ewing sarcoma. The study is designed to
establish initial safety and efficacy data in monotherapy and in combination with vincristine
to assess the potential of TK216 for further development.
Detailed Description
The study has been expanded to explore single agent TK216 for longer treatment duration.
Approximately 26 patients will be enrolled in this Cohort.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| TK216 treatment | Experimental | Dose escalation and expansion cohorts to determine dose-limiting toxicities, maximally tolerated dose, preliminary efficacy, and recommended phase 2 dose. | |
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed diagnosis of Ewing sarcoma (including ESFT)
in subjects with relapsed or refractory disease who have failed standard therapy
Exclusion Criteria:
- Symptomatic brain metastases
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 8 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Dose-limiting toxicities (DLTs) |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | Listing of dose-limiting toxicities by daily dose in mg/m^2 |
Secondary Outcome Measures
| Measure: | Adverse Events |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Antitumor activity as measured by Overall Response Rate (ORR) |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Antitumor activity as measured by Duration of Response (DOR) |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Disease Control |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Assay methods to detect EWS-FLI1 (or EWS-ERG and EWS-ets) |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacokinetics: Maximum Plasma Concentration [Cmax] |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacokinetics: Area Under the Curve [AUC] |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacokinetics: Halflife [T1/2] |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacodynamics: serum miRNA profile |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacodynamics: tumor tissue RNA assays |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
| Measure: | Pharmacodynamics: tumor tissue protein assays |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Oncternal Therapeutics, Inc |
Last Updated
August 23, 2021
