Ewing's sarcoma MedDRA version: 20.0 Level: PT Classification code 10015560 Term: Ewing's sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: DANYELZA
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Naxitamab
CAS Number: 1879925-92-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration
Sponsors
Institute of Mother and Child
Eligibility
Sex/Gender
All
Inclusion criteria
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 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. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 4 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 QTc >480 msec. 8. Symptoms of congestive heart failure or left ventricular ejection fraction 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 trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety assessment of the addition of naxitamab to standard 3-week chemotherapy (CHT) in patients with refractory Ewing's sarcoma (ES);Secondary Objective: To assess the clinical benefit of naxitamab add-on to the standard backbone IT chemotherapy and to estimate efficacy parameters that can be used for planning future phase III studies. To assess the impact of GD2 expression level on EFS and OS. Ancillary studies – biology studies: to evaluate the expression of GD2 in Ewing sarcoma cells in refractory/relapsed Ewing sarcoma patients. ;Primary end point(s): Safety and tolerability will be assessed based on an analysis of adverse events on all enrolled subjects. These events will be divided according to severity, seriousness, affected organ or system and analyzed for: •number of serious adverse events (SAE) •the number of adverse events (AE), including events of particular importance to the incidence and severity of adverse events occurring during treatment (TEAE) (encoded according to the preferred term and class of organ systems using the Medical Dictionary for Regulatory Activities (MedDRA); these events will be estimated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) •the result of a medical examination with the analysis of recorded vital signs •assessment of laboratory abnormalities according to NCI CTCAE v5.0 •assessment of heart rate, based on estimation of heart rate, atrioventricular conduction, QTcF interval and arrhythmia in a 12-lead ECG. ;Timepoint(s) of evaluation of this end point: throughout whole study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the efficacy of the use of naxitamab in combination with standard IT chemotherapy versus chemotherapy alone. • EFS – (Event-Free Survival), - from randomization to the date of disease progression, recurrence, second malignancy, death or to date of last follow-up for patients without events, • PFS (Progression-Free Survival), - from randomization to progression of the disease, • ORR (Overall Response Rate) - defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according WHO criteria, • OS (Overall Survival) - from randomization to subject’s death. ;Timepoint(s) of evaluation of this end point: throughout whole study | — |
Countries
Poland
Contacts
Public ContactHead of the Clinic
Department of Oncology and Oncological Surgery for Children and Adolescents
Outcome results
None listed