Efficacy and Tolerance Adjuvant High-Dose Thiotepa With Peripheral Stem Cell Rescue Associated With Conventional Chemotherapy in Children and Adults With Relapsed Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 23
- 主要终点
- Estimate the overall survival rate
研究概览
简要总结
Approximately 150 new cases of osteosarcoma are reported each year in France, of which 15 to 20% are metastatic.
Further to the initial standard care, about 45% of the patients relapse within a median duration of 20 months.
Result of the OS94 study results and of the investigation performed within the CRLCC, indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.
According to several studies, the 5-year overall survival rate of patients in first relapse is 23-28%,with a median post relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.
At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.
Thiotepa is known for its antitumor effect in numerous malignant tumors. In 2007, a study from our institution reported that about 35% of all osteosarcoma relapses are treated with a high-dose thiotepa while the efficacy and tolerance of this therapeutic strategy have never been assessed.
These results highlight the need to the evaluate the efficacy and tolerance of this high-dose of thiotepa within a clinical trial and its inclusion in the standard care of the osteosarcoma at relapse.
详细描述
Despite the absence of tumor registry, approximately 150 new cases of osteosarcoma are reported each year in France (100 cases per year in children and 50 cases in adults), of which 15 to 20% are metastatic. The standardized impact rate in the world population is estimated at 3 per million inhabitants per year.
Further to the initial standard care, about 45% of the patients relapse within a median interval of 20 months (range 3 months - 10 years).
Results of the OS94 study and of the investigation performed within the CRLCC indicate that 25 to 30 patients (children and adults) experience an osteosarcoma relapse each year in FRANCE.
Results of the five major published series indicate that the 5-year overall survival rate of patients in first relapse is between 23 and 28%, with a median post-relapse survival of 10 to 17 months. Multiple relapse cases are also reported in the COSS study, with a median time to second relapse of 0.8 year.
At present, there is no reference treatment for the standard care of osteosarcoma relapse in FRANCE.
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 Year 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 1 year and < 50 years
- •First osteosarcoma relapse, either local or metastatic, or second relapse after exclusive surgery NB: Whenever possible, only patients with histological evidence of relapse will be included.
- •Indication for chemotherapy confirmed by a multidisciplinary committee.
- •Surgical resection of all tumor sites must be possible, either as first-line therapy or after chemotherapy.
- •Lansky score ≥ 60%, or ECOG Performance Status ≤ 2
- •≥ 21-day interval after first-line chemotherapy
- •Blood tests, renal and liver functions within the normal range for age with, in particular, 7 days prior to study entry, blood or serum values as follows:
- •blood: neutrophil count > 1 G/L; platelets >100 G/L
- •renal: serum creatinine ≤ 1.5 x ULN depending on age; patients with serum creatinine values > 1.5 x ULN are eligible if creatinine clearance is > 70 mL/min/1.73 m²
- •liver: total bilirubin < 2 x ULN; ASAT and ALAT ≤ 5 x ULN
- •cardiac: isotopic or echographic Left Ventricular Ejection Fraction > 50 %.
- •Signed written informed consent; for children, signed consent from the patient (depending on age) and from the parents or legal representative is mandatory
- •Documented negative serum βHCG for female patients of childbearing age
- •Affiliation with health insurance.
排除标准
- •Patients with multiple relapses for whom surgical resection seems impossible, even after chemotherapy.
- •Patients already treated with high-dose chemotherapy regimens
- •Patients with a contra-indication to the treatment proposed
- •Patients not eligible for leukapheresis
- •Two-year follow-up impossible due to social, family, geographic or psychological reasons
- •Patient included in another protocol of clinical research
- •Pregnant or lactating women.
研究组 & 干预措施
experimental arm thiotepa
4 courses of conventional chemotherapy followed by high-dose Thiotepa with peripheral stem cell rescue. Surgical resection of all tumor masses will be performed as soon as possible.
干预措施: Thiotepa (Drug)
Reference arm
4 courses of conventional chemotherapy. Surgical resection of all tumor masses will be performed as soon as possible.
干预措施: Thiotepa (Drug)
结局指标
主要结局
Estimate the overall survival rate
时间窗: 24 months
次要结局
- Estimate overall survival after relapse diagnosis(24 months)
- Estimate the survival free progression after randomization(24 months)
- Evaluate the tolerance profile of experimental treatment (hematologic toxicity)(every 3 weeks)
- Estimate the rate of tumor response to treatment as assessed by conventional CT-scan(at inclusion, day 14-day 21 after the 2nd chemotherapy cycle, before randomization, day 14-day 21 after the 4th chemotherapy cycle, after thiotepa cure and 8 weeks after the end of treatment)
- Estimate histological response to treatment on surgical tumor samples(If surgery is applicable, a few weeks after thiotepa cure (12 to 17 weeks after inclusion))
- Study of biological and genomic properties and analysis of angiogenic markers correlated with relapse (optional)(At inclusion,at surgery , and at the end of treatment)