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TK216 in Patients With Relapsed or Refractory Ewing Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02657005
Recruitment Status : Recruiting
First Posted : January 15, 2016
Last Update Posted : May 26, 2021
Information provided by (Responsible Party):
Oncternal Therapeutics, Inc

Brief 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.

Condition or disease Intervention/treatment Phase
Sarcoma, Ewing Drug: TK216 Phase 1

Detailed Description:
The study is currently in the "expansion" phase after finding the recommended phase 2 dose in the dose/schedule escalation cohorts. Eighteen patients will be enrolled in the expansion phase. Vincristine is administered starting cycle 1, along with a 14 day continuous infusion of TK216.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Dose Escalation Study of Intravenous TK216 in Patients With Relapsed or Refractory Ewing Sarcoma
Actual Study Start Date : August 2016
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : June 2022

Arm Intervention/treatment
Experimental: TK216 treatment
Dose escalation and expansion cohorts to determine dose-limiting toxicities, maximally tolerated dose, preliminary efficacy, and recommended phase 2 dose.
Drug: TK216
Inhibitor of protein-protein interactions of EWS-FLI1 fusion protein

Primary Outcome Measures :
  1. Dose-limiting toxicities (DLTs) [ Time Frame: 18 months ]
    Listing of dose-limiting toxicities by daily dose in mg/m^2

  2. Maximum tolerated dose (MTD) [ Time Frame: 18 months ]
    Maximum daily dose in mg/m^2

  3. Biologically effective and recommended Phase 2 dose (RP2D) [ Time Frame: 18 months ]
    Daily dose in mg/m^2

Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: 18 months ]
  2. Antitumor activity as measured by Overall Response Rate (ORR) [ Time Frame: 18 months ]
  3. Antitumor activity as measured by Duration of Response (DOR) [ Time Frame: 18 months ]
  4. Duration of Disease Control [ Time Frame: 18 months ]
  5. Assay methods to detect EWS-FLI1 (or EWS-ERG and EWS-ets) [ Time Frame: 18 months ]
  6. Pharmacokinetics: Maximum Plasma Concentration [Cmax] [ Time Frame: 18 months ]
  7. Pharmacokinetics: Area Under the Curve [AUC] [ Time Frame: 18 months ]
  8. Pharmacokinetics: Halflife [T1/2] [ Time Frame: 18 months ]
  9. Pharmacodynamics: serum miRNA profile [ Time Frame: 18 months ]
  10. Pharmacodynamics: tumor tissue RNA assays [ Time Frame: 18 months ]
  11. Pharmacodynamics: tumor tissue protein assays [ Time Frame: 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02657005

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Contact: Oncternal Information 858-434-1113

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United States, California
UCLA Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Contact: Rubi Arias    310-794-0345   
Principal Investigator: Noah Federman, MD         
United States, Colorado
Children's Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Matthew O'hern, BS    720-777-8557    matthew.O'   
Principal Investigator: Margaret Macy, MD         
United States, District of Columbia
Children's National Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Ann Liew, MS    202-476-6755   
Principal Investigator: Aerang Kim, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10174
Contact: Paul Meyers, MD    833-675-5437   
Principal Investigator: Paul A Meyers, MD         
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Stephanie Weaver, RN, BSN    919-681-1883   
Contact: Lisa Hollon, RN, BSN    919-660-9217   
Principal Investigator: Richard Riedel, MD         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Peter Anderson, MD, PhD    216-308-2706   
Principal Investigator: Peter Anderson, MD, PhD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Phil Norr    503-494-0825   
Principal Investigator: Lara Davis, MD         
United States, Texas
Texas Children's Cancer & Hematology Centers, Baylor College Recruiting
Houston, Texas, United States, 77030
Contact: Kathy McCarthy, RN    832-824-4804   
Principal Investigator: Jade Wulff, MD         
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Joseph A Ludwig, MD    713-792-3626      
Contact: Gracy Zacharian    713-792-2669   
Principal Investigator: Joseph A Ludwig, MD         
Sponsors and Collaborators
Oncternal Therapeutics, Inc
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Study Director: James Breitmeyer, MD Oncternal Therapeutics
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Responsible Party: Oncternal Therapeutics, Inc Identifier: NCT02657005    
Other Study ID Numbers: TK216-01
First Posted: January 15, 2016    Key Record Dates
Last Update Posted: May 26, 2021
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue