Therapy-Optimization Trial and Phase II Study for the Treatment of Relapsed or Refractory of Primitive Neuroectodermal Brain Tumors and Ependymomas in Children and Adolescents
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 174
- 试验地点
- 54
- 主要终点
- P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course
研究概览
简要总结
The purpose of this study is to improve overall survival while maintaining a good quality of life in pediatric patients with refractory or recurrent brain tumors (medulloblastomas, supratentorial PNETs, ependymomas WHO grade II and III). Response to different chemotherapy options (intravenous versus oral chemotherapy, intraventricular chemotherapy) as part of a multimodal therapy will be assessed. Progression-free, overall survival and toxicity will be evaluated additionally.
详细描述
Parts of the study:
P-HIT-REZ-2005: a trial for the treatment of relapsed PNETs (medulloblastomas,supratentorial PNETs)
E-HIT-REZ-2005: a trial for the treatment of relapsed ependymomas (Phase II-Study with temozolomide)
Phase II-Study: intraventricular therapy with etoposide in neoplastic meningitis in relapsed PNETs and ependymomas with subarachnoid tumor manifestation (window study)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease Characteristics
- •Histologically confirmed Medulloblastoma, cerebral PNET or Ependymoma
- •Refractory or relapsed disease
- •Measurable disease by MRI or detection of tumor cells in cerebrospinal fluid Patients characteristics
- •Performance status ECOG ≥ 3 or Karnofsky Status ≥ 40%
- •Life expectancy ≥ 8 weeks
- •Hematological:
- •Absolute leukocyte count ≥ 2.0 x 10^9 /l
- •Hemoglobin ≥ 10g/dl
- •Platelet count ≥ 70 x 10^9/l
- •Creatinine no greater than 1.5 times UNL
- •No overt renal disease
- •Bilirubin less than 2.5 times UNL
- •AST and ALT less than 5 times UNL
- •No overt hepatic disease
- •No overt pulmonary disease
- •Cardiovascular:
- •No overt cardiovascular disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No uncontrolled infection Prior concurrent therapy
- •More than 2 weeks since prior systemic chemotherapy
- •More than 4 weeks since prior radiotherapy
- •No other concurrent anticancer or experimental drugs Examinations required
- •Examination of lumbar CSF
- •Cranial and spinal MRI within 14 days prior to start of treatment
排除标准
- 未提供
研究组 & 干预措施
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: carboplatin (Drug)
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: etoposide (Drug)
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: thiotepa, carboplatin, etoposide (Drug)
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: autologous stem cell transplantation (Procedure)
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: intraventricular etoposide (Drug)
1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
- high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or
- maintenance therapy with oral trofosfamide, etoposide
干预措施: trofosfamide, etoposide (Drug)
2: P-HIT-REZ 2005
oral chemotherapy with temozolomide, followed by
- high dose chemotherapy with temozolomide, thiotepa and autologous stem cell transplantation if patient have achieved a complete remission
- maintenance therapy with oral temozolomide or in case of progression with oral trofosfamide, etoposide
干预措施: temozolomide (Drug)
2: P-HIT-REZ 2005
oral chemotherapy with temozolomide, followed by
- high dose chemotherapy with temozolomide, thiotepa and autologous stem cell transplantation if patient have achieved a complete remission
- maintenance therapy with oral temozolomide or in case of progression with oral trofosfamide, etoposide
干预措施: temozolomide, thiotepa (Drug)
2: P-HIT-REZ 2005
oral chemotherapy with temozolomide, followed by
- high dose chemotherapy with temozolomide, thiotepa and autologous stem cell transplantation if patient have achieved a complete remission
- maintenance therapy with oral temozolomide or in case of progression with oral trofosfamide, etoposide
干预措施: autologous stem cell transplantation (Procedure)
2: P-HIT-REZ 2005
oral chemotherapy with temozolomide, followed by
- high dose chemotherapy with temozolomide, thiotepa and autologous stem cell transplantation if patient have achieved a complete remission
- maintenance therapy with oral temozolomide or in case of progression with oral trofosfamide, etoposide
干预措施: intraventricular etoposide (Drug)
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
干预措施: temozolomide (Drug)
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
干预措施: intraventricular etoposide (Drug)
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
干预措施: trofosfamide, etoposide (Drug)
Intraventricular Etoposide
Phase II, intraventricular chemotherapy with etoposide
干预措施: intraventricular etoposide (Drug)
结局指标
主要结局
P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course
时间窗: 4 months for each patient (8 years for the whole study population)
determination of objective repsonse rate (CR+PR)
E-HIT-REZ 2005 study (Phase II Study "Oral chemotherapy with temozolomide"): Evaluation of response rate to the 60-days oral chemotherapy with temozolomide
时间窗: 2 months for each patient (8 years for the whole study population)
determination of objective repsonse rate (CR+PR/all patients)
Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide
时间窗: 6 weeks for each patient (8 years for the whole study population)
disease stabilization rate (CR+PR+SD/all patients)
次要结局
- E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy(10 years)
- Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC)(8 years)
- P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy(10 years)
- P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms(8 years)
- E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC)(10 years)
研究者
Gudrun Fleischhack
MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
University Hospital, Essen