An International Clinical Program for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Ependymoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 536
- 试验地点
- 40
- 主要终点
- Gross Total Resection rate
研究概览
简要总结
The overall aim of this project is to improve the outcome of patients diagnosed with ependymoma by improving and harmonising the staging and the standard of care of this patient population and to improve the investigators understanding of the underlying biology thereby informing future treatment.
The program will evaluate new strategies for diagnosis (centralized reviews of pathology and imaging) and new therapeutic strategies in order to develop treatment recommendations.
Patients will be stratified into different treatment subgroups according to their age, the tumour location and the outcome of the initial surgery. Each subgroup will be studied in a specific randomised study to evaluate the proposed therapeutic strategies.
Stratum 1:
The aim of the stratum 1 is to evaluate the clinical impact of 16-week chemotherapy regimen with VEC-CDDP following surgical resection and conformal radiotherapy in terms of progression free survival in patients who are > 12 months and < 22 years at diagnosis, with completely removed intra cranial Ependymoma.
Stratum 2:
This stratum is designed as a phase II trial for patients who are > 12 months and < 22 years at diagnosis, with residual disease to investigate the possible activity of HD-MTX by giving to all patients the benefit of VEC chemotherapy whilst randomising half of patients to receive additional HD-MTX.
Patients will receive conformal radiotherapy (cRT). For patients who remain with a residual inoperable disease after induction chemotherapy and cRT, an 8 Gy boost of radiotherapy to the residual tumour will be delivered immediately after the end of the cRT.
Stratum 3 This stratum is designed as a phase II trial to evaluate the benefit of postoperative dose intense chemotherapy administered alone or in combination with valproate in children <12 months of age or those not eligible to receive radiotherapy .
详细描述
The Ependymoma Program is a comprehensive program to improve the accuracy of the primary diagnosis of ependymoma and explore different therapeutic strategies in children, adolescents and young adults, accordingly. This program is opened to all patients diagnosed with ependymoma below the age of 22 years.
It will include a centralised review of pre and post-operative imaging to assess the completeness of the resection.
It will also include a central review of pathology to confirm the histological diagnosis. The biological markers 1q and 6q gain, Tenascin C status, NELL2 and LAMA2, RELA-fusion and molecular subgroup by methylation array will be prospectively assessed for prospective evaluation of disease subgroups. Further biological evaluations will be coordinated within the linked BIOMECA study.
After surgery and central review of imaging and pathology, patients will be offered the opportunity to undergo second look surgery, if possible. Patients will be enrolled in one of 3 different strata according to the outcome of the initial surgical resection (residual disease vs no residual disease), their age or eligibility / suitability to receive radiotherapy. These 3 different strata correspond to 3 therapeutic strategies according to the patient status.
- Stratum 1 is designed as a randomised phase III study for patients who have had a complete resection, with no measurable residual disease (as confirmed by centrally reviewed MRI) and are > 12 months and < 22 years at diagnosis. Those patients will be randomised to receive conformal radiotherapy followed by either 16 weeks of chemotherapy with VEC-CDDP, or observation.
- Stratum 2 is designed as a randomised phase II study for patients who have inoperable measurable residual disease and who are > 12 months and < 22 years at diagnosis. Those patients will be randomised to two different treatment schedules of chemotherapy either with VEC or VEC+ high dose methotrexate (VEC +HD-MTX). After completion of the frontline chemotherapy, patients will be assessed for response (MRI) and will receive second look surgery when feasible. For those patients who remain unresectable with residual disease despite frontline chemotherapy and for whom second line surgery is not feasible, there will be a study of the safety of a radiotherapy boost of 8 Gy that will be administered to the residual tumour immediately after the completion of the conformal radiotherapy. Patients without evidence of residual disease after the chemotherapy and/or a second look surgery are not eligible for radiotherapy boost. All patients who have not shown progression under chemotherapy will receive, as maintenance therapy, a 16 week course of VEC -CDDP following completion of radiotherapy.
- Stratum 3 is designed as a randomised phase II chemotherapy study in children <12 months of age or those not eligible to receive radiotherapy. These patients will be randomised to receive a dose dense chemotherapy alternating myelosuppressive and relatively non-myelosuppressive drugs at 2 weekly intervals, with or without, the addition of the histone deacetylase inhibitor, valproate.
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
- — 至 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Stratum 1 arm A
Conformal radiotherapy followed by 16 weeks of VEC + CDDP.
干预措施: 16 weeks of VEC + CDDP (Drug)
Stratum 1 arm A
Conformal radiotherapy followed by 16 weeks of VEC + CDDP.
干预措施: Conformal radiotherapy (Radiation)
Stratum 1 arm B
Conformal radiotherapy.
干预措施: Conformal radiotherapy (Radiation)
Stratum 2 arm A
VEC + HD-MTX followed by conformal radiotherapy +/- boost
干预措施: VEC + HD-MTX (Drug)
Stratum 2 arm A
VEC + HD-MTX followed by conformal radiotherapy +/- boost
干预措施: conformal radiotherapy +/- boost (Radiation)
Stratum 2 arm B
VEC followed by conformal radiotherapy +/- boost
干预措施: VEC (Drug)
Stratum 2 arm B
VEC followed by conformal radiotherapy +/- boost
干预措施: conformal radiotherapy +/- boost (Radiation)
Stratum 3 arm A
Chemotherapy + Valproate.
干预措施: Chemotherapy + Valproate (Drug)
Stratum 3 arm B
Chemotherapy
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Gross Total Resection rate
时间窗: 3 years
Overall program, depends on the stratum (from 0.5 years to 3 years)
Progression-Free Survival
时间窗: from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 4.5 years
Number of treatment responders
时间窗: 15 months after final patient inclusion
Objective response to chemotherapy is measured based on SIOP-E Neuro Imaging guidelines.
次要结局
- Number of participants undergoing a second-look surgery(9 months)
- Overall Survival(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion)
- Quality of Survival(from date of randomization up to 5 years after the end of treatment)
- Evaluation of neuropsychological morbidity(from date of randomization up to 5 years after the end of treatment)
- Comparison of neuroendocrine morbidity(from date of randomization up to 5 years after the end of treatment)
- Number of participants with adverse events as a measure of safety and tolerability(from date of randomization up to 5 years after the end of treatment)
- Radiotherapy-free survival rate(from date of randomization until the date of first documented progression or date of death from any cause, or radiotherapy intervention, whichever came first, up to 2.5 years after the final patient inclusion)
- Efficacy in each molecular sub-group(from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3 years after the final patient inclusion)
- Concordance between central and local radiological assessment of the efficacy of post-operative chemotherapy(15 months after final patient inclusion)