MEMMAT - Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial - A Phase II study of metronomic and targeted anti-angiogenesis therapy for children with recurrent/progressive medulloblastoma, ependymoma, ATRT and rare CNS tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 24
- 主要终点
- π: probability for response, lack of recurrence after gross total resection. Stratum II+III: H0: π≤15% study therapy is considered as ineffective (type I error rate α=0.05, two sided). H1: π≥35% study therapy is considered as effective (type II error rate β=0.10 in Stratum I, β=0.20 in Stratum II+III). Stratum IV: H0: π1≤ π2 study therapy is considered as equal or inferior (type I error rate α=0.025, one sided). H1: π1>π2 study therapy is consididered as superior (type II error rate β=0.20)
研究概览
简要总结
To determine the response rate defined as the percentage of patients with CR, PR, SD or lack of recurrence at 6 months after start of antiangiogenic treatment (stratum II, III, V). To determine whether temozolomide, irinotecan, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt can increase the response rate after 6 months of treatment, compared with etoposid, cyclophosphamide, bevacizumab, thalidomide, celecoxib, fenofibrate, etoposide ivt, cytarabine ivt (stratum IV).
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Stratum I: Relapsed or progressive medulloblastoma (at least one site of untreated recurrent disease) - completed
- •Stratum IV: Confirmation of the medulloblastoma group by methylation; IDAT (raw data of methylation array)
- •Stratum V: Relapsed or progressive CNS tumor of various histologies or patients with exclusion criteria or adult patients (explorative)
- •Stratum II: Relapsed or progressive ependymoma (at least one site of untreated recurrent disease)
- •Stratum III: Relapsed or progressive ATRT (at least one site of untreated recurrent disease)
- •Histological confirmation of medulloblastoma/ependymoma/ATRT at diagnosis or relapse
- •Female or male, aged from 0 to <20 years (at time of original diagnosis)
- •Participants must have normal organ and bone marrow function (ALT <5x institutional upper limit of normal, creatinine <1.5x institutional upper limit of normal for age, WBC >1000/mm3, platelets > 20,000/mm
- •Patients with values less than WBC 2000/mm3 or platelets 50,000/mm3 will require initiation of treatment with etoposide and cyclophosphamide at a lower starting dose as defined within the protocol.
- •Karnofsky performance status ≥
- •For infants and children less than 12 years of age, the Lansky play scale ≥50% will be used
- •Written informed consent of patients and / or parents
- •Stratum IV: Relapsed or progressive medulloblastoma (at least one site of untreated recurrent disease)
排除标准
- •Active infection
- •Anticipation of the need for major elective surgery during the course of the study treatment
- •Any disease or condition that contraindicates the use of the study medication/treatment or places the patient at an unacceptable risk of experiencing treatment-related complications
- •Stratum IV: Prior treatment with temozolomide/irinotecan (can be included in Stratum V)
- •Previously non-irradiated patients should be evaluated for radiotherapy
- •Non-healing surgical wound
- •A bone fracture that has not satisfactorily healed
- •VP- or subduroperitoneal shunt dependency (can be included in Stratum V)
- •Pregnancy or breast feeding
- •Treatment for current relapse (surgery may be performed before antiangiogenic treatment; patients with sites of disease not irradiated are still eligible for the protocol)
- •Known hypersensitivity to any of the drugs in the protocol
- •Active peptic ulcer
- •Any significant cardiovascular disease not controlled by standard therapy e.g. systemic hypertension
结局指标
主要结局
π: probability for response, lack of recurrence after gross total resection. Stratum II+III: H0: π≤15% study therapy is considered as ineffective (type I error rate α=0.05, two sided). H1: π≥35% study therapy is considered as effective (type II error rate β=0.10 in Stratum I, β=0.20 in Stratum II+III). Stratum IV: H0: π1≤ π2 study therapy is considered as equal or inferior (type I error rate α=0.025, one sided). H1: π1>π2 study therapy is consididered as superior (type II error rate β=0.20)
π: probability for response, lack of recurrence after gross total resection. Stratum II+III: H0: π≤15% study therapy is considered as ineffective (type I error rate α=0.05, two sided). H1: π≥35% study therapy is considered as effective (type II error rate β=0.10 in Stratum I, β=0.20 in Stratum II+III). Stratum IV: H0: π1≤ π2 study therapy is considered as equal or inferior (type I error rate α=0.025, one sided). H1: π1>π2 study therapy is consididered as superior (type II error rate β=0.20)
次要结局
- Kaplan Meier survival estimates of overall survival rates after 6, 12, 24, and 36 months with 95% confidence intervals will be evaluated and compared to historical samples
- Kaplan Meier estimates of progression free survival after 6, 12, 24, and 36 months with 95% confidence intervals will be evaluated and compared to historical samples
- The number and relative frequency of toxicities (CTCAE Version 5.0 grade 3, 4 and 5) will be evaluated every 12 weeks.
- Performance status will be compared from the start of therapy and every 12 weeks
- Subscale-scores and total scores of the KINDL assessments at the start of therapy, after 6 months 12 months, 18 months and 24 months of therapy will be evaluated. PRO will be evaluated every two weeks.
- The aforementioned variables will be evaluated comparing their influence on response rate, overall survival rate, progression free survival rate, toxicity, quality of life and performance status by multivariate cox-regression
- Examination of predictive and prognostic factors will be descriptive.
研究者
Intensive Care Medicine and Neuropediatrics
Scientific
Medical University Of Vienna