An Open-label, Single-arm, Phase II Study to Evaluate Safety and Efficacy of Doxorubicin in Combination With Radiotherapy, Temozolomide and Valproic Acid in Patients With Glioblastoma Multiforme (GBM) and Diffuse Intrinsic Pontine Glioma (DIPG)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Time to early discontinuation of the study drug (doxorubicin)
研究概览
简要总结
The standard therapy of glioblastoma (GBM) consists of gross total resection followed by focal irradiation to the tumor bed with concomitant and adjuvant temozolomide (TMZ). The association of valproic acid and TMZ during radiotherapy improves survival of GBM. Preclinical studies suggested that doxorubicin had a strong antineoplastic activity against human gliomas. Moreover, some studies showed that the continuous infusion of anthracyclines in patients with solid tumor ensured a better safety profile compared with bolus administration.
Based on these findings, the purpose of this study is to evaluate safety and efficacy of prolonged administration of doxorubicin in combination with radiotherapy, temozolomide and valproic acid in pediatric and adult patients with newly diagnosed GBM and diffuse intrinsic pontine glioma (DIPG).
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
- 3 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females patients, aged >3 years and < 30 years;
- •Newly diagnosed of GBM, DIPG, diffuse brainstem glioma, diffuse spinal glioma, bilateral thalamic glioma, gliomatosis cerebri, anaplastic astrocytoma;
- •Patients undergone either surgery or biopsy only;
- •No prior chemotherapy and/or radiotherapy;
- •Life expectancy ≥ 4 weeks;
- •Karnofsky/Lansky ≥ 40 %;
- •Written informed consent obtained from the patient/parents or legal representative;
- •Adequate hematological function (leucocyte ≥ 2.0 x 10^9/l -Hemoglobin ≥ 10 g/dl - platelet ≥ 50 x 10^9 /l);
- •Adequate liver function (total bilirubin ≤ 2.5 x ULN - ALT/AST ≤ 5.0 x ULN);
- •Adequate renal function (serum creatinine ≤ 1.5 x ULN);
- •Adherence to trial treatment and compliance with the protocol
排除标准
- •Any disease or condition that contraindicates the use of the study drug (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy)
- •Prior anti-cancer therapy
- •Pregnancy or breastfeeding
- •Non adequate contraception
研究组 & 干预措施
Doxorubicin
Patients are treated with Weller-Stupp protocol: initial radiotherapy (1.8 Gy/die, days 1-5; total dose 54-60 Gy) with concomitant oral temozolomide (75mg/m2/die, days 1-7) per 6 weeks.
At week 10 (4 weeks after the chemo-radiotherapy treatment completion): 1 cycle of oral temozolomide (150-180 mg/m2, days 1-5)
At week 14 (8 weeks after the chemo-radiotherapy treatment completion) 1 cycle of prolonged infusion of Doxorubicin (25mg/m2/die in 24 hours, days 1-4; total cumulative dose 100 mg/m2).
At week 18 (4 weeks after the end of doxorubicin administration): 16 cycles of oral temozolomide (initial dose of 150 mg/m2 increasing to 180 mg/m2 days 1-5, 28-day cycle).
Oral valproic acid (20-30 mg/Kg/die bid) is administered from week 1 until the last treatment day.
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Time to early discontinuation of the study drug (doxorubicin)
时间窗: 6 months
Number of patients who undergone to withdrawal of doxorubicin
时间窗: 6 months
Rate of early suspension of the study drug (doxorubicin)
Number of participants with treatment-related serious adverse events (SAE) as assessed by CTCAE v4.0
时间窗: 32 months
Number of patients with SAE and SAE leading to withdrawal from the study
Number of patients who died for SAE as assessed by CTCAE v4.0
时间窗: 32 months
Mortality due to adverse events
次要结局
- Progression free survival(2 months)
- Event free survival(2 months)
- Overall survival(2 months)
- Rate of treatment response(2 months)
研究者
Iacopo Sardi
MD, PhD
Meyer Children's Hospital IRCCS