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

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: NCT05968768
Recruitment Status : Recruiting
First Posted : August 1, 2023
Last Update Posted : January 17, 2024
Wroclaw Medical University
Information provided by (Responsible Party):
Anna Raciborska, Institute of Mother and Child, Warsaw, Poland

Brief Summary:
Prospective, interventional, open, randomized, national, multicenter, non-commercial trial

Condition or disease Intervention/treatment Phase
Ewing Sarcoma Drug: Naxitamab Phase 2

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma
Actual Study Start Date : October 24, 2023
Estimated Primary Completion Date : May 1, 2027
Estimated Study Completion Date : July 31, 2028

Arm Intervention/treatment
Experimental: Experimental - Naxitamab Arm
Treatment with naxitamab will be continued no longer than 6 cycles a year or until disease progression, patient consent, unacceptable toxicities, or study closure
Drug: Naxitamab
Naxitamab will be used only in a hospital setting and must be administered under the supervision of a doctor with experience in the use of oncological therapies. The medicinal product must be administered by a healthcare professional prepared to deal appropriately with severe allergic reactions, including anaphylaxis, in an environment that provides immediate, full access to resuscitation. The patient should have 2 well-functioning IV accesses before any naxitamab treatment is initiated. The solution should be administered through a peripheral or central intravenous catheter. Other concomitant intravenous medicinal products should be administered through separate intravenous access. Before the start of each infusion, premedication will be carried out.
Other Name: danyelza

No Intervention: Control Group - standard treatment
The control group - will receive only standard treatment.

Primary Outcome Measures :
  1. Safety assessment of the addition of naxitamab to standard 3-week chemotherapy (CHT) in patients with refractory Ewing's sarcoma (ES) [ Time Frame: up to 240 days ]
    Safety will be assessed by number of serious adverse events (SAE), by the number of adverse events (AE), by medical examination with the analysis of recorded vital signs, laboratory abnormalities according to NCI CTCAE v5.0

Secondary Outcome Measures :
  1. Event-Free Survival (EFS ) [ Time Frame: 3 years ]
    Will be measured from randomization to death, disease progression or recurrence, or secondary malignancy, whichever comes first

  2. Progression-Free Survival (PFS) [ Time Frame: 1 year ]
    from randomization to progression of the disease

  3. Overall Response Rate (ORR) [ Time Frame: 126 days ]
    Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR),

  4. Overall Survival (OS) [ Time Frame: 3 years ]
    Will be measured from randomization to subject's death

Information from the National Library of Medicine

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.

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically proven Ewing sarcoma of the bone or soft tissues.
  2. Subject's archival tumour sample (formalin-fixed, paraffin-embedded; FFPE) available for evaluation of GD2 expression.
  3. Documented disease progression (during or after completion of at least one line treatment) 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 trial protocol BUTTERFLY version 1.0 of 30.09.2022 r.anti-neoplastic therapy at the discretion of the investigator.
  9. Signing of informed consent for trial participation (including for naxitamab treatment) according with current legal regulations.
  10. Consent to the use of effective contraception throughout the period of the study and a minimum of 1 year after discontinuation of study treatment in patients at puberty and sexual maturity

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 and naxitamab).
  5. Simultaneous treatment with other drugs which might interact with naxitamab or IT regimen.
  6. Persistent toxicity related to prior therapy, making it impossible to treat with naxitamab.
  7. Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, 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, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
  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 or breastfeeding.
  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 or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the tri

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): NCT05968768

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Contact: Anna Raciborska, Prof. +48 22 32 77 205

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Mother and Child Institute Recruiting
Warsaw, Mazowian, Poland, 01-211
Contact: Katarzyna Maleszewska    +48 22 32 77 205   
Principal Investigator: Anna Raciborska, Prof         
Wroclaw Medical University Not yet recruiting
Wrocław, Poland, 50-556
Contact: Anna Jodłowska-Kopacz    48 71 733 27 92   
Principal Investigator: Marek Ussowicz, Prof.         
Sponsors and Collaborators
Anna Raciborska
Wroclaw Medical University
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Principal Investigator: Anna Raciborska, Prof. the Institue of Mother and Child
Publications of Results:

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Responsible Party: Anna Raciborska, Prof Ass, Institute of Mother and Child, Warsaw, Poland Identifier: NCT05968768    
Other Study ID Numbers: Butterfly
First Posted: August 1, 2023    Key Record Dates
Last Update Posted: January 17, 2024
Last Verified: January 2024

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Anna Raciborska, Institute of Mother and Child, Warsaw, Poland:
Ewing Sarcoma
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue