TK216 in Patients With Relapsed or Refractory Ewing Sarcoma
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|ClinicalTrials.gov Identifier: NCT02657005|
Recruitment Status : Terminated
First Posted : January 15, 2016
Last Update Posted : June 22, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Sarcoma, Ewing||Drug: TK216||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||85 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: TK216 treatment
Dose escalation and expansion cohorts to determine dose-limiting toxicities, maximally tolerated dose, preliminary efficacy, and recommended phase 2 dose.
Inhibitor of protein-protein interactions of EWS-FLI1 fusion protein
- Dose-limiting toxicities (DLTs) [ Time Frame: 18 months ]Listing of dose-limiting toxicities by daily dose in mg/m^2
- Maximum tolerated dose (MTD) [ Time Frame: 18 months ]Maximum daily dose in mg/m^2
- Biologically effective and recommended Phase 2 dose (RP2D) [ Time Frame: 18 months ]Daily dose in mg/m^2
- 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
- Adverse Events [ Time Frame: 18 months ]
- Antitumor activity as measured by Overall Response Rate (ORR) [ Time Frame: 18 months ]
- Antitumor activity as measured by Duration of Response (DOR) [ Time Frame: 18 months ]
- Duration of Disease Control [ Time Frame: 18 months ]
- Assay methods to detect EWS-FLI1 (or EWS-ERG and EWS-ets) [ Time Frame: 18 months ]
- Pharmacokinetics: Maximum Plasma Concentration [Cmax] [ Time Frame: 18 months ]
- Pharmacokinetics: Area Under the Curve [AUC] [ Time Frame: 18 months ]
- Pharmacokinetics: Halflife [T1/2] [ Time Frame: 18 months ]
- Pharmacodynamics: serum miRNA profile [ Time Frame: 18 months ]
- Pharmacodynamics: tumor tissue RNA assays [ Time Frame: 18 months ]
- Pharmacodynamics: tumor tissue protein assays [ Time Frame: 18 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||8 Years and older (Child, Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
- 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.
- Must have a central venous catheter in place prior to initiating infusion of study drug.
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.
- 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.
- Stem Cell Transplant or Rescue without TBI: No evidence of active graft vs. host disease and ≥ 3 months must have elapsed since transplant.
- 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.
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 in patients ≥17 years old; or Karnofsky/Lansky >50 in patients <16 years old.
- Life expectancy of at least 3 months.
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
|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|
|Study Director:||James Breitmeyer, MD||Oncternal Therapeutics|
|Responsible Party:||Oncternal Therapeutics, Inc|
|Other Study ID Numbers:||
|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|
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neuroectodermal Tumors, Primitive
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue