Apatinib in Combination With Ifosfamide and Etoposide (IE) for Relapsed or Refractory Osteosarcoma Progressed Upon First-line Chemotherapy (AIEO): a Prospective, Multiple-centre, Two-arm, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 4
- 主要终点
- Progression free survival
研究概览
简要总结
Apatinib has led to positive responses in the treatment of osteosarcoma refractory to first-line chemotherapy. However, apatinib demonstrates only short-lived activity, and the disease control of musculoskeletal lesions is worse than that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). We have ever retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centers in China and concluded that for osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. However to overcome the influence of other interventions on the outcome, we are currently performing a prospective trial to investigate this combination, from which more accurate data on this treatment strategy are expected.
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
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •advanced recurrent and refractory osteosarcoma confirmed by histopathology;
- •initial treatment in the Orthopedic/Oncology Departments of Peking University People's Hospital or Peking University Shougang Hospital;
- •progression less than 6 months after first-line chemotherapy with a combination of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide (first-line chemotherapy);
- •measurable lesions according to the Response Evaluation Criteria for Solid Tumors (RECIST 1.1) ;
- •Eastern Cooperative Oncology Group performance status ≤ 1 ;
- •acceptable haematologic, hepatic, and renal function.
排除标准
- •those who had been previously treated with antiangiogenic TKIs and single IE chemotherapy;
- •those who had severe or uncontrolled medical disorders that could jeopardize the outcomes of the study. These confounding conditions included, cardiac clinical symptoms or disease with left ventricular ejection fraction<50%, and hypertension that could not be well controlled with antihypertensive drugs.;
- •all patients were assessed by the sarcoma board including a thoracic surgeon with at least 10 years surgical experience. Patients with lung metastases only were carefully assessed for eligibility for metastasectomy, of whom those who were suitable for surgery were excluded from this study;
- •weight loss of 20% or more before illness;
- •brain or leptomeningeal metastasis;
- •surgical procedure or radiotherapy within 4 weeks of enrollment;
- •activegastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
- •proteinuria or hematuria, denutrition with albuminemia <25 g/L;
- •women who were pregnant or breast feeding, other malignancy;
- •positive HBV/HCV/HIV serology, and known allergy to the experimental agents.
研究组 & 干预措施
Apatinib+IE group
IE: Ifosfamide Plus Etoposide
干预措施: Apatinib+IE (Drug)
IE group
IE: Ifosfamide Plus Etoposide
干预措施: IE (Drug)
结局指标
主要结局
Progression free survival
时间窗: 2 years
from the start of target treatment until disease progression or death, whichever came first.
次要结局
- Overall survival(3 years)
研究者
Xie Lu
Musculoskeletal Tumor Center
Peking University People's Hospital