Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Patients With High-grade, Operable, Non-metastatic Osteosarcoma of the Extremity
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 738
- 试验地点
- 1
- 主要终点
- Event-Free Survival
研究概览
简要总结
Preclinical models show that a daily antiangiogenic regimen at low-dose may be effective against chemotherapy-resistant tumors. The aim of this study is to evaluate the efficacy of maintenance therapy with continuous oral cyclophosphamide and methotrexate in patients with high grade, operable, non-metastatic osteosarcoma (OST) of the extremities. The primary end point is event-free survival (EFS) from randomization.
详细描述
The study design includes a backbone of 10 weeks of preoperative therapy using MAP (High-dose methotrexate, cisplatin, and doxorubicin). Following surgery, non-metastatic patients were randomized by blocks to complete 31 weeks of MAP or to receive 73 weeks of maintenance therapy following MAP; while metastatic patients received maintenance therapy in combination with MAP since the beginning of treatment.
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
- 1 Day 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with high-grade malignancy osteosarcoma , biopsy-proven , newly diagnosed , previously untreated . Patients with osteosarcoma as a second malignancy should also be eligible .
- •Patients with any primary site , with or without metastases at diagnosis , will be accepted and treated.
- •Patients < 30 years.
- •Patients must have normal body function and adequate renal function defined as serum creatinine < 1.5 x the normal value or creatinine clearance > 60ml/min/1 ,73m2 .
- •Patients must have adequate hepatic function, defined as total bilirubin < 1.5 x normal, aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) < 2.5 x normal.
- •Patients must have adequate cardiac function defined by a shortening fraction > 27 % by echocardiogram or ejection fraction > 47 % by radioisotopic angiogram .
- •If pre- chemotherapy amputation is necessary, the patient is included in the study and eligible to survival analyzes, however the pathological analyze response will be not performed.
- •Obtain material for pathological and molecular study is recommended .
- •Whenever possible a central catheter should be placed against the intensity of chemotherapy and need for forced hydration .
- •Patient or legal guardian must sign a consent form which will be explain the type of treatment and procedures that the patient will be submitted .
- •Time > than 4 weeks between biopsy and initiation of treatment - Restaging
排除标准
- •Disease progression ( increase of at least 20% of the extent of the lesion, taking as reference the smallest measurement recorded from the start of treatment, or the appearance of one or more lesions );
- •Any properly documented clinical situation , which at the discretion of the attending physician , patient can not follow with chemotherapy , for safety reasons ;
- •The evaluation of cardiac aspects will be done carefully , so will exclude patients with 20% reduction in the ejection fraction of the left ventricle compared to baseline or with a ventricular ejection fraction < 45 % regardless of baseline;
- •The patient refusal to continue treatment ;
- •Nephrotoxicity , neurotoxicity and ototoxicity grade 4 ;
- •Delay greater than 40 days for the realization of the next treatment cycle , not related to toxicity;
- •Refusal of surgery ; 8 . Variation above 20% of the recommended dose without justification.
研究组 & 干预措施
Maintenance therapy
73 weeks of continuous oral low dose chemotherapy with cyclophosphamide (CPM) and methotrexate (MTX) following 31 weeks of MAP.
干预措施: continuous oral cyclophosphamide and methotrexate (Drug)
结局指标
主要结局
Event-Free Survival
时间窗: EFS AT 5 YEARS
AT 5 YEARS
次要结局
- Overall survival(OS AT 5 YEARS)
研究者
Antônio Sérgio Petrilli
MD, PhD
Grupo de Apoio ao Adolescente e a Crianca com Cancer