TK216 in Patients With Relapsed or Refractory Ewing Sarcoma

Sarcoma, Ewing Clinical Trial

Official title:

A Phase 1 / 2, Dose Escalation Study of Intravenous TK216 in Patients With Relapsed or Refractory Ewing Sarcoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02657005
• Other study ID #: TK216-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2016
• Est. completion date: June 2022

Study information

• Verified date: June 2022
• Source: Oncternal Therapeutics, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The study has been expanded to explore single agent TK216 for longer treatment duration. Approximately 26 patients will be enrolled in this Cohort.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 85
• Est. completion date: June 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

1. Willing and able to provide written IRB/IEC-approved Informed Consent. For patients < 18 years of age, their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.

2. Have histologically or cytologically confirmed diagnosis of Ewing sarcoma (including ESFT) with relapsed or refractory disease. Patients with metastatic disease who had standard chemotherapy at the time of diagnosis Pathology reports and slides or blocks should be available for review or additional testing. If not available, site must discuss with Sponsor.

3. Measurable disease according to RECIST version 1.1. Measurable disease can be verified from a previously documented computed tomography (CT) scan or MRI as long as no anti-cancer treatments have been administered in the interim.

4. Must have a central venous catheter in place prior to initiating infusion of study drug.

5. Prior cancer therapy:

Patients may have received no more than 5 prior systemic regimens. At the time of treatment initiation, at least 2 weeks or 5 half-lives, whichever is longer, must have elapsed since prior cytotoxic chemotherapy. At least 7 days must have elapsed since completion of any prior non-cytotoxic cancer therapy.

6. Prior radiotherapy is allowed If = 4 weeks has elapsed for radiation therapy (RT); = 6 months must have elapsed if prior total body irradiation, craniospinal RT or if > 50% radiation of the pelvis; > 6 weeks must have elapsed if other substantial bone marrow radiation. Patients who have received brain irradiation must have completed whole brain radiotherapy and/or gamma knife at least 4 weeks prior to enrollment.

7. Stem Cell Transplant or Rescue without TBI: No evidence of active graft vs. host disease and = 3 months must have elapsed since transplant.

8. Patients with controlled asymptomatic CNS involvement are allowed (see Concomitant Medications). Patients not requiring steroids or requiring steroids at stable dose (= 4 mg/day dexamethasone or equivalent) for at least 2 weeks are eligible.

9. Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to NCI CTCAE (Version 4.03) Grade < 1. Details can be provided by Sponsor.

10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 in patients =17 years old; or Karnofsky/Lansky >50 in patients <16 years old.

11. Life expectancy of at least 3 months.

Related Conditions & MeSH terms

• Neuroectodermal Tumors, Primitive, Peripheral
• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• TK216
Inhibitor of protein-protein interactions of EWS-FLI1 fusion protein

Locations

Country	Name	City	State
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Duke Cancer Institute	Durham	North Carolina
United States	Texas Children's Cancer & Hematology Centers, Baylor College	Houston	Texas
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Oncternal Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities (DLTs)	Listing of dose-limiting toxicities by daily dose in mg/m^2	18 months
Primary	Maximum tolerated dose (MTD)	Maximum daily dose in mg/m^2	18 months
Primary	Biologically effective and recommended Phase 2 dose (RP2D)	Daily dose in mg/m^2	18 months
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE.	Daily dose of 175 mg/m2/day of TK216 administered intravenously via continuous infusion over 28-days	12 months
Secondary	Adverse Events		18 months
Secondary	Antitumor activity as measured by Overall Response Rate (ORR)		18 months
Secondary	Antitumor activity as measured by Duration of Response (DOR)		18 months
Secondary	Duration of Disease Control		18 months
Secondary	Assay methods to detect EWS-FLI1 (or EWS-ERG and EWS-ets)		18 months
Secondary	Pharmacokinetics: Maximum Plasma Concentration [Cmax]		18 months
Secondary	Pharmacokinetics: Area Under the Curve [AUC]		18 months
Secondary	Pharmacokinetics: Halflife [T1/2]		18 months
Secondary	Pharmacodynamics: serum miRNA profile		18 months
Secondary	Pharmacodynamics: tumor tissue RNA assays		18 months
Secondary	Pharmacodynamics: tumor tissue protein assays		18 months