Ewing SarcomaPhase 2NCT05968768
To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma (Butterfly)
A Phase 2 study testing Naxitamab in people with Ewing Sarcoma, run by Anna Raciborska at 2 sites in Poland.
Trial summary
Prospective, interventional, open, randomized, national, multicenter, non-commercial trial Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Ewing Sarcoma
- What is being tested?
- Naxitamab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesPoland
- Study dates
- 24 Oct 2023to 31 Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically proven Ewing sarcoma of the bone or soft tissues.
- Subject's archival tumour sample (formalin-fixed, paraffin-embedded; FFPE) available for evaluation of GD2 expression.
- Documented disease progression (during or after completion of at least one line treatment) or any subsequent recurrence.
- GD2 positive tumor assessed by IHC.
- Age ≥ 2 years and ≤ 21 years.
- Life expectancy of at least 12 weeks from the time informed consent was signed.
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- Previous systemic anticancer treatment completed ≥ 3 weeks, major surgery ≥ 2 weeks, and radiation therapy ≥ 4 weeks prior to study enrollment.
- 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.
- Signing of informed consent for trial participation (including for naxitamab treatment) according with current legal regulations.
- 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
Who cannot join
- Failure to meet any of the inclusion criteria.
- Not eligible to IT.
- Previous treatment with an anti-GD2 antibody.
- Hypersensitivity to the study drugs or any of their ingredients (covers IT and naxitamab).
- Simultaneous treatment with other drugs which might interact with naxitamab or IT regimen.
- Persistent toxicity related to prior therapy, making it impossible to treat with naxitamab.
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- Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening corrected QT interval (QTc) >480 msec.
- Symptoms of congestive heart failure or left ventricular ejection fraction <50%.
- 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.
- Requirement, or likely requirement, for corticosteroids at doses >10 mg prednisolone (or equivalent) per day or other immunosuppressive agents.
- Diagnosis of other malignancies before study inclusion.
- Planning to become pregnant (while being treated with IT or naxitamab), pregnancy or breastfeeding.
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Poland2 sites, 2 recruiting
- Recruiting
Mother and Child Institute
Warsaw, Mazowian, 01-211
Katarzyna Maleszewska, +48 22 32 77 205, klinika.onkologii@imid.med.pl
Anna Raciborska, Prof
- Not yet recruiting
Wroclaw Medical University
Wroclaw, 50-556
Anna Jodłowska-Kopacz, 48 71 733 27 92, badaniakliniczne@usk.wroc.pl
Marek Ussowicz, Prof.
About this study
Official title: To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma
Prospective, interventional, open, randomized, national, multicenter, non-commercial trial
Read the detailed description
The study includes:
- 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.
- 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).
- 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.
- Patients will be recalculated according to the intent to treat (ITT) rule.
- The study will be conducted in accordance to GCP and after EC approval of the protocol.
- Conditions
- Ewing Sarcoma
- Being tested
- Naxitamab
- Keywords
- Ewing Sarcoma
- Medical subject headings
- Sarcoma, Ewing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaxitamabDrug
Also called danyelza
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental - Naxitamab Arm | Experimental | Treatment with naxitamab will be continued no longer than 6 cycles a year or until disease progression, patient consent, unacceptable toxicities, or study closure Receives: Drug: Naxitamab |
| Control Group - standard treatment | No intervention | The control group - will receive only standard treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessment of the addition of naxitamab to standard 3-week chemotherapy (CHT) in patients with refractory Ewing's sarcoma (ES)
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
Measured: up to 240 days
Secondary outcomes (4)
Event-Free Survival (EFS )
Will be measured from randomization to death, disease progression or recurrence, or secondary malignancy, whichever comes first
Measured: 3 years
Progression-Free Survival (PFS)
from randomization to progression of the disease
Measured: 1 year
Overall Response Rate (ORR)
Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR),
Measured: 126 days
Overall Survival (OS)
Will be measured from randomization to subject's death
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start24 Oct 2023
- Primary completion1 May 2027 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Ewing SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anna Raciborska
- Sponsor type
- University, hospital or other
- Collaborators
- Wroclaw Medical University
- Responsible party
- Sponsor-investigator, Anna Raciborska, Institute of Mother and Child, Warsaw, Poland
- Investigators
- Anna Raciborska, Prof., Principal investigator, the Institue of Mother and Child
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05968768
- Sponsor's protocol ID
- Butterfly
- Status last verified
- Oct 2026
- First submitted
- 13 Jun 2023
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nakajima M, Guo HF, Hoseini SS, Suzuki M, Xu H, Cheung NV. Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody. Pediatr Blood Cancer. 2021 Jul;68(7):e28971. doi: 10.1002/pbc.28971. Epub 2021 Apr 12.
PubMed 33844437Chan GC, Chan CM. Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma. Biomolecules. 2022 Feb 24;12(3):358. doi: 10.3390/biom12030358.
PubMed 35327550Musumeci F, Cianciusi A, D'Agostino I, Grossi G, Carbone A, Schenone S. Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma. Molecules. 2021 Nov 23;26(23):7069. doi: 10.3390/molecules26237069.
PubMed 34885651Wingerter A, El Malki K, Sandhoff R, Seidmann L, Wagner DC, Lehmann N, Vewinger N, Frauenknecht KBM, Sommer CJ, Traub F, Kindler T, Russo A, Otto H, Lollert A, Staatz G, Roth L, Paret C, Faber J. Exploiting Gangliosides for the Therapy of Ewing's Sarcoma and H3K27M-Mutant Diffuse Midline Glioma. Cancers (Basel). 2021 Jan 29;13(3):520. doi: 10.3390/cancers13030520.
PubMed 33572900Nazha B, Inal C, Owonikoko TK. Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy. Front Oncol. 2020 Jul 7;10:1000. doi: 10.3389/fonc.2020.01000. eCollection 2020.
PubMed 32733795Hensel J, Metts J, Gupta A, Ladle BH, Pilon-Thomas S, Mullinax J. Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy. Cancer J. 2022 Jul-Aug 01;28(4):322-327. doi: 10.1097/PPO.0000000000000603.
PubMed 35880942Mora J. Autologous Stem-Cell Transplantation for High-Risk Neuroblastoma: Historical and Critical Review. Cancers (Basel). 2022 May 24;14(11):2572. doi: 10.3390/cancers14112572.
PubMed 35681553
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma
- ClinicalTrials.gov ID
- NCT05968768
- Acronym / sponsor ID
- Butterfly
- Conditions
- Ewing Sarcoma
- Keywords
- Ewing Sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Anna RaciborskaUniversity, hospital or other
- Collaborators
- Wroclaw Medical University
- Study start
- 24 Oct 2023 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 31 Jul 2028 (estimated)
- First posted
- 1 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, interventional, open, randomized, national, multicenter, non-commercial trial
Detailed description
The study includes:
- 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.
- 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).
- 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.
- Patients will be recalculated according to the intent to treat (ITT) rule.
- The study will be conducted in accordance to GCP and after EC approval of the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental - Naxitamab Arm | Experimental | Drug: NaxitamabTreatment with naxitamab will be continued no longer than 6 cycles a year or until disease progression, patient consent, unacceptable toxicities, or study closure |
| Control Group - standard treatment | No intervention | –The control group - will receive only standard treatment. |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Histologically proven Ewing sarcoma of the bone or soft tissues.
- Subject's archival tumour sample (formalin-fixed, paraffin-embedded; FFPE) available for evaluation of GD2 expression.
- Documented disease progression (during or after completion of at least one line treatment) or any subsequent recurrence.
- GD2 positive tumor assessed by IHC.
- Age ≥ 2 years and ≤ 21 years.
Key exclusion criteria (13 listed)
- Failure to meet any of the inclusion criteria.
- Not eligible to IT.
- Previous treatment with an anti-GD2 antibody.
- Hypersensitivity to the study drugs or any of their ingredients (covers IT and naxitamab).
- Simultaneous treatment with other drugs which might interact with naxitamab or IT regimen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NaxitamabAlso: danyelzaNaxitamab 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. | Drug | Experimental - Naxitamab Arm |
Primary outcome
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
4 secondary outcomes
Event-Free Survival (EFS )
Time frame: 3 years
Progression-Free Survival (PFS)
Time frame: 1 year
Overall Response Rate (ORR)
Time frame: 126 days
Overall Survival (OS)
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Results publication: PubMed 33844437Nakajima M, Guo HF, Hoseini SS, Suzuki M, Xu H, Cheung NV. Potent antitumor effect of T cells armed with anti-GD2 bispecific antibody. Pediatr Blood Cancer. 2021 Jul;68(7):e28971. doi: 10.1002/pbc.28971. Epub 2021 Apr 12.
- Results publication: PubMed 35327550Chan GC, Chan CM. Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma. Biomolecules. 2022 Feb 24;12(3):358. doi: 10.3390/biom12030358.
- Results publication: PubMed 34885651Musumeci F, Cianciusi A, D'Agostino I, Grossi G, Carbone A, Schenone S. Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma. Molecules. 2021 Nov 23;26(23):7069. doi: 10.3390/molecules26237069.
- Results publication: PubMed 33572900Wingerter A, El Malki K, Sandhoff R, Seidmann L, Wagner DC, Lehmann N, Vewinger N, Frauenknecht KBM, Sommer CJ, Traub F, Kindler T, Russo A, Otto H, Lollert A, Staatz G, Roth L, Paret C, Faber J. Exploiting Gangliosides for the Therapy of Ewing's Sarcoma and H3K27M-Mutant Diffuse Midline Glioma. Cancers (Basel). 2021 Jan 29;13(3):520. doi: 10.3390/cancers13030520.
- Results publication: PubMed 32733795Nazha B, Inal C, Owonikoko TK. Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy. Front Oncol. 2020 Jul 7;10:1000. doi: 10.3389/fonc.2020.01000. eCollection 2020.
- Results publication: PubMed 35880942Hensel J, Metts J, Gupta A, Ladle BH, Pilon-Thomas S, Mullinax J. Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy. Cancer J. 2022 Jul-Aug 01;28(4):322-327. doi: 10.1097/PPO.0000000000000603.
- Results publication: PubMed 35681553Mora J. Autologous Stem-Cell Transplantation for High-Risk Neuroblastoma: Historical and Critical Review. Cancers (Basel). 2022 May 24;14(11):2572. doi: 10.3390/cancers14112572.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Raciborska, Prof. principal investigator
the Institue of Mother and Child
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naxitamab in people with Ewing Sarcoma, run by Anna Raciborska at 2 sites in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Raciborska, Prof. (+48 22 32 77 205, klinika.onkologii@imid.med.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05968768, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.