Chemo-immunotherapy in Patients Under 18 Years of Age With Bone and Soft Tissue Sarcomas

Phase 3

Recruiting

Conditions: Bone Sarcoma
Embryonal Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma

Brief Summary: Data from 40 patients are planned to be included in the study to randomize approximately 10 patients.
...

Detailed Description: Data from 40 patients are planned to be included in the study to randomize approximately 10 patients.
...

Recruitment & Eligibility

Inclusion Criteria

Signed written informed consent form;
Age under 18 years of age;
Histologically confirmed GD2-positive osteogenic sarcoma, Ewing's sarcoma, soft tissue and undifferentiated sarcomas;
Prior to study enrollment, patients must have been treated with one or more lines of adequate chemotherapy and must have relapsed on this therapy or have refractoriness to it;
General satisfactory condition of the patient (Lansky scale activity 80-100% (children under 16 years of age), Karnofsky scale 80-100% (children over 16 years of age); ECOG - 0-1);
Sufficient cardiopulmonary reserves of the patient's organism (ECG (ELECTROCARDIOGRAPHY) data within normal limits, ventricular ejection fraction > 75% of the upper limit of normal;
Adequate liver function (ALT (ALANINE AMINOTRANSFERASE) ≤ 2.5 * VGN, AST (ASPARTATE AMINOTRANSFERASE) ≤ 2.5 * VGN), kidney (creatinine <1.5 * VGN), red bone marrow (granulocytes> 2.0 * 109/L, platelets> 150 * 109/L).

Six months later, two additional criteria were formulated:
Life expectancy at the time of initiation of therapy within the framework of the study is not less than 12 months
Oligometastasis disease (presence of 1 to 5 distant metastatic foci) at restaging at the time of the decision to include the patient in the study;

Arm && Interventions

Group	Intervention	Description
Generalized / metastatic GD2-positive osteosarcoma	dinutuximab beta	Generalized / metastatic GD2-positive osteosarcoma after progression on 1st line of chemotherapy. • ICE(IFOSFAMIDE+CARBOPLATIN+ETOPOSIDE), IE (IFOSFAMIDE+ETOPOSIDE), CARBOPLATIN+ ETOPOSIDE, Аi(DOXORUBICIN+IFOSFAMIDE), IFO(IFOSFAMIDE), GEM/TAX(GEMCITABINE+DOCETAXEL) (osteosarcoma) + 6 consecutive cycles of dinutuximab beta immunotherapy
Generalized / metastatic GD2-positive rhabdomyosarcoma	dinutuximab beta	Generalized / metastatic GD2-positive rhabdomyosarcoma after progression on 1st line of chemotherapy. Chemotherapy options: • CARBO(CARBOPLATIN) + ETO(ETOPOSIDE), IFO(IFOSFAMIDE) + ETO(ETOPOSIDE), CARBO(CARBOPLATIN) + IFO(IFOSFAMIDE) (rhabdomyosarcoma) + 6 consecutive cycles of dinutuximab beta immunotherapy
Generalized / metastatic GD2-positive Ewing sarcoma	dinutuximab beta	Generalized / metastatic GD2-positive Ewing sarcoma after progression on 1st line of chemotherapy. • ICE (IFOSFAMIDE+CARBOPLATIN+ETOPOSIDE), TEM(TEMOZOLOMIDE+IRINOTECAN), VCT(VINCRISTINE+CYCLOPHOSPHAN+TOPOTECAN), TC(CYCLOPHOSPHAN+TOPOTECAN), TT(TEMOZOLOMIDE+TOPOTECAN), GEM/TAX(GEMCITABINE+DOCETAXEL) (Ewing's sarcoma) + 6 consecutive cycles of dinutuximab beta immunotherapy

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	6 months	PFS will be assessed from the date of the first induction dose of dinutuximab beta to the date of first documented disease progression or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	6 months	OS will be assessed from the date of administration of the first induction dose of dinutuximab beta to the date of death.
Overall response rate (ORR)	6 months	ORR will be assessed by tumor response CR or PR.
Tumor control rate (TCR)	6 months	TCR will be assessed by tumor response according CR + PR + stabilization.
Duration of response (DR)	6 months	DR will be assessed from initial response to disease progression.
Immune-associated adverse events (IAAE)	6 months	IAAE will be assessed from the date of administration of the first induction dose of dinutuximab beta to the date of death.