Efficacy and Safety of Intra-arterial Cisplatin Plus Anti-angiogenesis Inhibitor Rh-endostatin (Endostar) Combined With Systematic Chemotherapy in Osteosarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of tumor response
研究概览
简要总结
The goal of this clinical trial is to learn the efficacy and safety of intra-arterial cisplatin plus anti-angiogenesis inhibitor rh-endostatin (Endostar) combined with systematic chemotherapy in osteosarcoma. The main questions it aims to answer are:
- Is it safe when rh-endostatin and cisplatin are administered intra-arterially?
- Does intra-arterial cisplatin plus rh-endostatin increase the rate of tumor necrosis compared with traditional treatment?
Researchers will treat newly diagnosed osteosarcoma patients with systematic treatment and local treatment.
For systematic treatment, regular high-dose methotrexate and adriamycin will be administered intravenously.
For local treatment, rh-endostatin was administered intra-arterially with dosage of 150 mg for a 6-h continuous infusion; then cisplatin was administered intra-arterially at 120 mg/m2 as a 6-h continuous infusion.
Local treatment is conducted by insertion of a catheter percutaneously using the Seldinger technique through the brachial or femoral artery under local anesthesia.
Participants will:
• Receive local combined with systematic treatment once every 2-3 weeks for 2-4 cycles before surgery.
详细描述
Osteosarcoma (OS) is the most common bone cancer in children and young adolescents. Despite the emergence of new therapeutic modalities such as targeted therapy and immunotherapy, chemotherapy remains the standard treatment. The current standard treatment for osteosarcoma is the preoperative chemotherapy, surgery and postoperative chemotherapy. Preoperative chemotherapy (or neoadjuvant chemotherapy) and neoadjuvant chemotherapeutic agents include cisplatin, adriamycin, methotrexate. The use of preoperative chemotherapy has increased the 5-year survival rate from 20% to 60%-70%. Over the past 40 years, limited progress has been made in improving survival outcomes in patients with OS.
Transcatheter arterial infusion (TAI) is the direct infusion of drugs in the tumor blood supply artery, which can overcome the physiological barrier that some intravenous drug can not pass, thus significantly increasing the local drug concentration in the tumor and improving the therapeutic efficacy. Studies have shown that the combination of intravenous doxorubicin and intra-arterial cisplatin infusion before surgery resulted in a favorable histological response in 87% of enrolled patients, with a 10-year survival rate of 93% and an event-free survival rate of 86%.
Recombinant endostatin, an anti-angiogenic drug approved by the National Medical Products Administration of China in 2005 for the treatment of non-small cell lung cancer. In preclinical studies, synergistic antitumor efficacy was observed in an osteosarcoma mouse model with the addition of rh-endostatin to doxorubicin. In the clinical study of osteosarcoma, after comparing 58 patients with stage IIB osteosarcoma treated with chemotherapy combined with endostatin and 272 patients treated with chemotherapy alone, results show that the 5-year DMFS (distant metastasis-free survival) of the control group (61%) was significantly lower than that of the rh-endostatin group (79%) (P = 0.013). The 5-year OS of the control group (74%) was significantly lower than that of the rh-endostatin treatment group (87%) (P = 0.029). These results suggest that endostatin combined with chemotherapy for osteosarcoma significantly improves distant metastasis-free survival, with tolerable adverse effects, and is worthy of further clinical investigation.
Therefore, the investigators propose that arterial infusion of endostatin and cisplatin combined with systematic therapy might improve the treatment efficacy in preoperative course.
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
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of osteosarcoma patients aged 12-40 years old;
- •Accept to receive treatment with neoadjuvant chemotherapy regimen and completing the standard treatment course; Voluntary informed consent, joining the study with good compliance.
- •Have detailed medical data (such as medical history data, laboratory reports of blood routine and liver and kidney functions, pathology reports, etc.), and complete records of postoperative follow-up.
排除标准
- •Combined history of acute injury, infection and surgery in the last 3 months;
- •Those with severe liver and kidney function abnormalities;
- •Those who are using anti-inflammatory drugs;
- •Pre-existing hematologic diseases before treatment;
- •Combined with other malignant tumors;
- •Diagnosed with autoimmune disease or using steroid drugs for more than 1 month before treatment;
- •Suffering from mental illness or cognitive dysfunction.
研究组 & 干预措施
IA cisplatin plus endostatin
Intra-arterial cisplatin plus anti-angiogenesis inhibitor rh-endostatin (Endostar) combined with systematic chemotherapy
干预措施: intra-arterial cisplatin plus anti-angiogenesis inhibitor rh-endostatin (Endostar) (Drug)
结局指标
主要结局
Incidence of tumor response
时间窗: From enrollment to the end of treatment at 1 month
according to tumor cell necrosis rate (TCNR) of tumor tissue sample after surgery.
Incidence of Treatment-Emergent Adverse Events
时间窗: From enrollment to the end of treatment at 1-month
Safety analysis (adverse events) according to CTCAE 5.0
次要结局
- Microvessel density(From enrollment to the end of treatment at 1 month)
研究者
Hong-Tao Li
Principal Investigator
Shanghai 6th People's Hospital