A Randomized, Multicenter, Open-label Phase III Study of Dinutuximab Beta With Investigator's Choice of Chemotherapy in Patients Under 18 Years of Age With Bone and Soft Tissue Sarcomas With High Levels of GD2 Expression and Disease Progression During 1st Line Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Data from 40 patients are planned to be included in the study to randomize approximately 10 patients.
This study involves patients with advanced/metastatic GD2-positive rhabdomyosarcoma after progression on 1st line of chemotherapy, advanced/metastatic GD2-positive Ewing sarcoma after progression on 1st line of chemotherapy and advanced/metastatic GD2-positive osteosarcoma after progression on 1st line of chemotherapy.
All patients will receive therapy until disease progression (a total of 6 courses of immunotherapy).
The primary objective of the study is to determine the efficacy and safety of dinutuximab beta with investigator's choice of chemotherapy.
详细描述
Data from 40 patients are planned to be included in the study to randomize approximately 10 patients.
This study involves patients with advanced/metastatic GD2-positive rhabdomyosarcoma after progression on 1st line of chemotherapy, advanced/metastatic GD2-positive Ewing sarcoma after progression on 1st line of chemotherapy and advanced/metastatic GD2-positive osteosarcoma after progression on 1st line of chemotherapy.
6 cycles of treatment with dinutuximab beta are provided in combination with 6-8 cycles of chemotherapy during the induction therapy phase. Switching from one chemotherapy regimen to another is not allowed. Dinutuximab beta should be administered as a slow intravenous infusion through a separate catheter using an infusion pump.
All patients will receive therapy until disease progression (a total of 6 courses of immunotherapy).
Treatment response will be assessed by the investigator after 2, 4 cycles of treatment and at the end of the reinduction therapy period (i.e., after 6 cycles of dinutuximab beta treatment and 6 - 8 cycles of polychemotherapy). Treatment response will be assessed by tumor response according to the criteria for response assessment in the treatment of solid tumors (RECIST 1.1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Participant Group/Arm
- Generalized / metastatic GD2-positive rhabdomyosarcoma after progression on 1st line of chemotherapy.
- Generalized / metastatic GD2-positive Ewing sarcoma after progression on 1st line of chemotherapy.
- Generalized / metastatic GD2-positive osteosarcoma after progression on 1st line of chemotherapy.
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •Withdrawal of consent by the patient or his/her parent/guardian.
- •Exclusion of the patient by the investigator for safety or ethical reasons.
研究组 & 干预措施
Generalized / metastatic GD2-positive rhabdomyosarcoma
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
干预措施: dinutuximab beta (Drug)
Generalized / metastatic GD2-positive Ewing sarcoma
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
干预措施: dinutuximab beta (Drug)
Generalized / metastatic GD2-positive osteosarcoma
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
干预措施: dinutuximab beta (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 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.
次要结局
- Overall survival (OS)(6 months)
- Overall response rate (ORR)(6 months)
- Tumor control rate (TCR)(6 months)
- Duration of response (DR)(6 months)
- Immune-associated adverse events (IAAE)(6 months)