To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma (Butterfly)

Last updated: April 9, 2025
Sponsor: Anna Raciborska
Overall Status: Active - Recruiting

Phase

2

Condition

Sarcoma

Ewing's Family Tumors

Sarcoma (Pediatric)

Treatment

Naxitamab

Clinical Study ID

NCT05968768
Butterfly
  • Ages 2-21
  • All Genders

Study Summary

Prospective, interventional, open, randomized, national, multicenter, non-commercial trial

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Histologically proven Ewing sarcoma of the bone or soft tissues.

  2. Subject's archival tumour sample (formalin-fixed, paraffin-embedded; FFPE) availablefor evaluation of GD2 expression.

  3. Documented disease progression (during or after completion of at least one linetreatment) or any subsequent recurrence.

  4. GD2 positive tumor assessed by IHC.

  5. Age ≥ 2 years and ≤ 21 years.

  6. Life expectancy of at least 12 weeks from the time informed consent was signed.

  7. Previous systemic anticancer treatment completed ≥ 3 weeks, major surgery ≥ 2 weeks,and radiation therapy ≥ 4 weeks prior to study enrollment.

  8. Recovered from adverse effects of prior surgery, radiotherapy, or Clinical trialprotocol BUTTERFLY version 1.0 of 30.09.2022 r.anti-neoplastic therapy at thediscretion of the investigator.

  9. Signing of informed consent for trial participation (including for naxitamabtreatment) according with current legal regulations.

  10. Consent to the use of effective contraception throughout the period of the study anda minimum of 1 year after discontinuation of study treatment in patients at pubertyand sexual maturity

Exclusion

Exclusion Criteria:

  1. Failure to meet any of the inclusion criteria.

  2. Not eligible to IT.

  3. Previous treatment with an anti-GD2 antibody.

  4. Hypersensitivity to the study drugs or any of their ingredients (covers IT andnaxitamab).

  5. Simultaneous treatment with other drugs which might interact with naxitamab or ITregimen.

  6. Persistent toxicity related to prior therapy, making it impossible to treat withnaxitamab.

  7. Significant cardiac conduction abnormalities, including known familial prolonged QTsyndrome, or screening corrected QT interval (QTc) >480 msec.

  8. Symptoms of congestive heart failure or left ventricular ejection fraction <50%.

  9. Inadequate pulmonary function defined as evidence of dyspnea at rest, exerciseintolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinicallyindicated.

  10. Requirement, or likely requirement, for corticosteroids at doses >10 mg prednisolone (or equivalent) per day or other immunosuppressive agents.

  11. Diagnosis of other malignancies before study inclusion.

  12. Planning to become pregnant (while being treated with IT or naxitamab), pregnancy orbreastfeeding.

  13. Other acute or persistent disorders, behaviors or abnormal laboratory test results,which might increase the risk related to the participation in this clinical trial orto taking the study drug, or which might influence the interpretation of the studyresults, or which, in the investigator's opinion, disqualify a patient fromparticipating in the tri

Study Design

Total Participants: 24
Treatment Group(s): 1
Primary Treatment: Naxitamab
Phase: 2
Study Start date:
October 24, 2023
Estimated Completion Date:
July 31, 2028

Study Description

The study includes:

  1. Biology screening: to estimate expression on GD2 on Ewing sarcoma cells from tumor tissue from archival material. Availability of tumor tissue is required for pre-screening testing to determine GD2 expression. To be screened for potential enrollment into the study patients or their legal representatives must have signed the pre-screening informed consent form (ICF) to consent to using their archival tumor sample to test the expression of GD2 in their tumor. The expression level of GD2 will be characterized in tumor tissue by immunohistochemistry (IHC) at a local and a central diagnostic testing laboratory.

  2. Standard stratifying diagnostic tests (laboratory assessment: morphology, blood chemistry including ALT, AST, eGFR, creatinine, sodium, potassium, coagulation, urine analysis including pH, blood, protein, leukocytes, glucose, urobilinogen, bilirubin, ketones, nitrites, specific gravity, vital signs (body temperature, systolic and diastolic blood pressure, and pulse rate), ECG, cardiac function test, imaging test: CT/MRI scan).

  3. Patients with GD2 expression will be randomized in proportions (2:1) to the experimental (D) and control groups (S). The cohort D will consist of 16 subjects, the cohort S 8 subjects. The exploratory cohort D will receive the experimental regimen in 3-week cycles consisting of irinotecan given intravenously (iv) 50 mg/m2 after oral temozolomide 100 mg/m2 on days 1-5 and naxitamab administered iv 2.25 mg/kg/day over 30 - 60 minutes, days 2, 4, 8 and 10 (up to 150 mg/day; total 9 mg/kg per cycle), and GM-CSF 250 mg/m2/day subcutaneously, days 6-10. Patients randomized to arm S will receive IT alone. Treatment cycles will be repeated every 21 days summary to 6 cycles or until disease progression, or subsequent relapsed, or occurrence of intolerable toxicity, or any event making impossible treatment continuation, or investigator's judgment, or withdrawal of consent. All activities are presented in Schedule of Assessments (SoA) at the end of the study synopsis.

  4. Patients will be recalculated according to the intent to treat (ITT) rule.

  5. The study will be conducted in accordance to GCP and after EC approval of the protocol.

Connect with a study center

  • Mother and Child Institute

    Warsaw, Mazowian 01-211
    Poland

    Active - Recruiting

  • Wroclaw Medical University

    Wrocław, 50-556
    Poland

    Site Not Available

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