A Phase II Study of Gemcitabine-docetaxel Chemotherapy With Anti-angiogenic Therapy for Pulmonary Resectable Metastases of Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- 12 months Progression-free survival rate(12mPFR)
研究概览
简要总结
The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma.
详细描述
After standard chemotherapy and surgery for the localized disease, pulmonary metastases of osteosarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib is a oral kinase inhibitor of receptor tyrosine targeting VEGFR2. A pilot study indicated that Apatinib improved the PFS after multi-line chemotherapy failure, and might partly reversed chemo-refractory status for advanced osteosarcoma. Thus, the investigators explored the efficacy of combining Apatinib with current available second-line chemotherapy compared to chemotherapy alone for treating first resectable pulmonary metastases of osteosarcoma following the failure of first-line chemotherapy and wide/radical-margin surgery. Participants will receive 250 mg of apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the surgical resection of the pulmonary metastases. Osteosarcoma patients with pulmonary recurrence only at baseline will be recruited in the study. The primary end point is progression-free survival rate (PFR) compared with historical control. A12 month PFR of 30% or less is considered inactive, while a 12 month PFR of 50% or greater is regarded as of interest for additional development. With a type I error rate of 5% and a power of 83%, the number of patients needed for this design is 43.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
An Independent radiologic reviewing committee assess the radiological tumor response in a blinded manner. Data Safety and Monitoring Board (DSMB) access the outcome in the interim analysis and final analysis
入排标准
- 年龄范围
- 10 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age between 10 and 50 years;
- •diagnosis of histologically confirmed high grade osteosarcoma;
- •identification of pulmonary metastases without the existence of local recurrence(previous re-resection of local recurrence with wide margin is allowed).
- •resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
- •prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy
- •wide/radical-margin surgical resection of the primary tumor completed at least 4 weeks before enrollment.
- •Eastern Cooperative Oncology Group(ECOG) performance status 0-2 with a life expectancy >3 months;
- •adequate renal, hepatic, and hemopoietic function;
- •normal or controlled blood pressure;
- •no thoracic comorbidities with adequate pulmonary function eligible for thoracic surgery
排除标准
- •previously exposed to GD chemotherapy or VEGFR2 Tyrosine-kinase inhibitors (TKIs);
- •existence of local recurrence;
- •have had other kinds of malignant tumors at the same time;
- •cardiac insufficiency or arrhythmia;
- •uncontrolled complications, such as diabetes mellitus and so on;
- •coagulation disorders or Hemorrhagic diseases ;
- •metastases considered unresectable or borderline resectable at baseline
- •intolerable of thoracis surgery
- •pleural or peritoneal effusion that needs to be handled by surgical treatment;
- •combined with other infections or wounds
- •wound dystrophy, poor soft-tissue around implantation or other wound complications risky of non-healing given angiogenesis inhibitor assessed by the investigators
研究组 & 干预措施
Apatinib + GD group
Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection.
干预措施: Apatinib (Drug)
Apatinib + GD group
Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection.
干预措施: GD regimen (Drug)
结局指标
主要结局
12 months Progression-free survival rate(12mPFR)
时间窗: 12 months from the recruitment of the study
The proportion of patients with progression-free survival at 12 months according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). A 12mPFR of 30% or less is considered inactive, while a 12mPFR of 50% or greater is regarded as of interest for additional development
次要结局
- Overall survival (OS)(Baseline until death, followed through study completion, an average of 2 years)
- Total resectability(after neoadjuvant systemic therapy, an average of 8~9 weeks)
- Progression free survival (PFS)(Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years))
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](through study completion, an average of 1 years)
- Objective response rate (ORR)(after neoadjuvant systemic therapy, an average of 8~9 weeks)
- Clinical benefit rate (CBR)(after neoadjuvant systemic therapy, an average of 8~9 weeks)
- OS rate(12 and 24 months from baseline)
研究者
Weibin Zhang, MD, PhD.
Professor
Ruijin Hospital