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

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Primary Purpose

Status

Not yet recruiting

Phase

Phase 2

Locations

Poland

Study Type

Interventional

Intervention

Naxitamab

About this trial

This is an interventional treatment trial for Ewing Sarcoma focused on measuring Ewing Sarcoma

Eligibility Criteria

2 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. 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 Exclusion Criteria: 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. 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

Sites / Locations

Mother and Child Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Experimental - Naxitamab Arm

Control Group - standard treatment

Arm Description

Treatment with naxitamab will be continued no longer than 6 cycles a year or until disease progression, patient consent, unacceptable toxicities, or study closure

The control group - will receive only standard treatment.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Event-Free Survival (EFS )

Will be measured from randomization to death, disease progression or recurrence, or secondary malignancy, whichever comes first

Progression-Free Survival (PFS)

from randomization to progression of the disease

Overall Response Rate (ORR)

Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR),

Overall Survival (OS)

Will be measured from randomization to subject's death

Full Information

NCT ID

NCT05968768

First Posted

June 13, 2023

Last Updated

July 28, 2023

Sponsor

Anna Raciborska

Collaborators

Wroclaw Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05968768

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

August 10, 2023 (Anticipated)

Primary Completion Date

May 1, 2027 (Anticipated)

Study Completion Date

July 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Anna Raciborska

Collaborators

Wroclaw Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ewing Sarcoma

Keywords

Ewing Sarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental - Naxitamab Arm

Arm Type

Experimental

Arm Description

Treatment with naxitamab will be continued no longer than 6 cycles a year or until disease progression, patient consent, unacceptable toxicities, or study closure

Arm Title

Control Group - standard treatment

Arm Type

No Intervention

Arm Description

The control group - will receive only standard treatment.

Intervention Type

Drug

Intervention Name(s)

Naxitamab

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety assessment of the addition of naxitamab to standard 3-week chemotherapy (CHT) in patients with refractory Ewing's sarcoma (ES)

Description

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

Time Frame

up to 240 days

Secondary Outcome Measure Information:

Title

Event-Free Survival (EFS )

Description

Will be measured from randomization to death, disease progression or recurrence, or secondary malignancy, whichever comes first

Time Frame

3 years

Title

Progression-Free Survival (PFS)

Description

from randomization to progression of the disease

Time Frame

1 year

Title

Overall Response Rate (ORR)

Description

Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR),

Time Frame

126 days

Title

Overall Survival (OS)

Description

Will be measured from randomization to subject's death

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: 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. 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 Exclusion Criteria: 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. 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

Facility Information:

Facility Name

Mother and Child Institute

City

Warsaw

State/Province

Mazowian

ZIP/Postal Code

01-211

Country

Poland

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Katarzyna Maleszewska

Phone

+48 22 32 77 205

Email

klinika.onkologii@imid.med.pl

First Name & Middle Initial & Last Name & Degree

Anna Raciborska, Prof

12. IPD Sharing Statement

Citations:

PubMed Identifier

33844437

Citation

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.

Results Reference

result

PubMed Identifier

35327550

Citation

Chan 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 Reference

result

PubMed Identifier

34885651

Citation

Musumeci 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 Reference

result

PubMed Identifier

33572900

Citation

Wingerter 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 Reference

result

PubMed Identifier

32733795

Citation

Nazha 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 Reference

result

PubMed Identifier

35880942

Citation

Hensel 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 Reference

result

PubMed Identifier

35681553

Citation

Mora 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.

Results Reference

result

Ewing Sarcoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial