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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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02657005
Recruitment Status : Terminated
First Posted : January 15, 2016
Last Update Posted : June 22, 2022
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 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 / 2, Dose Escalation Study of Intravenous TK216 in Patients With Relapsed or Refractory Ewing Sarcoma
Actual Study Start Date : August 2016
Actual Primary Completion Date : May 2022
Actual 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

  4. Number of participants with treatment-related adverse events as assessed by CTCAE. [ Time Frame: 12 months ]
    Daily dose of 175 mg/m2/day of TK216 administered intravenously via continuous infusion over 28-days

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

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 ClinicalTrials.gov identifier (NCT number): NCT02657005

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United States, California
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Hospital
Washington, District of Columbia, United States, 20010
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10174
United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Texas
Texas Children's Cancer & Hematology Centers, Baylor College
Houston, Texas, United States, 77030
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
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
ClinicalTrials.gov Identifier: NCT02657005    
Other Study ID Numbers: TK216-01
First Posted: January 15, 2016    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
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