Prospective, interventional, open, randomized, national, multicenter, non-commercial trial
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
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.
Mother and Child Institute
Warsaw, Mazowian, Poland
RECRUITINGWroclaw Medical University
Wroclaw, Poland
NOT_YET_RECRUITINGSafety 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
Time frame: up to 240 days
Event-Free Survival (EFS )
Will be measured from randomization to death, disease progression or recurrence, or secondary malignancy, whichever comes first
Time frame: 3 years
Progression-Free Survival (PFS)
from randomization to progression of the disease
Time frame: 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),
Time frame: 126 days
Overall Survival (OS)
Will be measured from randomization to subject's death
Time frame: 3 years
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