SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- survival
研究概览
简要总结
STUDY DESIGN:
Prospective, non-randomised multicentre study with patients stratified according to risk groups INVESTIGATIONAL MEDICINAL PRODUCTS The IMPs on this trial are Carboplatin, Cisplatin, Ifosfamide and Etoposide (as approved by German competent authority).
PRIMARY OBJECTIVES:
Germinoma
- To maintain current high event-free survival (EFS) rates using a risk adapted approach
- In localised germinoma: to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
- In bifocal tumours (pineal + suprasellar): to treat as non-metastatic disease and to omit whole brain and spinal irradiation by using combined treatment with standard chemotherapy and ventricular irradiation (+/- boosts)
- In metastatic disease: to maintain current excellent EFS in metastatic germinoma with craniospinal irradiation Malignant non-germinoma
To improve EFS:
- by dose escalation of chemotherapy in patients identified as high risk at diagnosis ( age < 6 years and/or AFP serum / CSF > 1000 ng/ml)
- by standardising the surgical approach for residual disease after treatment Teratoma
- To register patients and collect data regarding diagnostics, treatment and outcome in order to develop future treatment strategies
SECONDARY OBJECTIVES:
Germinoma
- To minimise long term effects of irradiation by sparing spinal and whole brain radiotherapy in non-metastatic disease Malignant non-germinoma
- In standard risk to maintain EFS with chemotherapy and local irradiation Teratoma
- To evaluate the influence of surgery and treatment on outcome to assist in the development of a fu-ture treatment strategy For all histological subtypes
- To improve accuracy of diagnosis and staging in all registered patients
- To standardise neurosurgical intervention
- For all patients requiring biopsy or resection according to protocol guidelines, to collect and to store tumour material, and CSF where possible, for use in future biological studies.
ENDPOINTS / Criteria for evaluation:
Main end point
Event-free survival, defined as minimum time from the date of diagnosis to:
- Death from any cause
- Relapse
- Progressive disease on therapy
- Or second malignancy
Secondary end points
- Overall survival, defined as time to death from any cause, measured from the date of diagnosis
- Short and long term toxicity.
详细描述
PATIENT POPULATION Age of patients: no lower or upper age limit; Estimated number: 400 malignant germ cell tumours
Diagnosis and main criteria for inclusion/exclusion:
Intracranial Germ Cell tumours of any histology and intracranial site and dissemination
Inclusion criteria
- Main residence in one of the participating countries
- Primary diagnosis of an intracranial germ cell tumour
- Written consent for trial participation, treatment according to the protocol and consent for data trans-fer
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main residence in one of the participating countries
- •Primary diagnosis of an intracranial germ cell tumour
- •Written consent for trial participation, treatment according to the protocol and consent for data transfer
排除标准
- •Tumour entity other than primary intracranial germ cell tumour or CNS GCT as second malignancy
- •Primary diagnosis pre-dating the opening of SIOP CNS GCT II in the participating country of registration
- •Medical, psychiatric or social conditions incompatible with trial treatment or treatment according to protocol is not intended
- •Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc.
- •Pregnancy and lactation
- •Any treatment not given according to protocol prior to registration
研究组 & 干预措施
Germinoma metastatic
• Metastatic or incompletely staged germinomas (± teratoma) Do not receive chemotherapy in this protocol
Radiotherapy
- Metastatic or incompletely staged pure germinoma 24 Gy (15 fractions) to craniospinal axis with a 16 Gy (10 fraction) boost to tumour bed and any intracranial metastases and spinal deposits (total tumour dose 40 Gy)
- Metastatic germinoma plus teratoma (incompletely resected) 24 Gy (15 fractions) to craniospinal axis ; 30.4 Gy (19 fraction) boost to tumour bed and 16 Gy (10 frac-tion) boost to metastases (total tumour dose 54.4 Gy)
干预措施: craniospinal irradiation (Radiation)
germinoma non-metastatic
Chemotherapy:
• Non-metastatic fully staged germinoma (± teratoma) Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide Note: Bifocal germinoma (pineal+suprasellar) are treated as non-metastatic germinoma, if staging shows no additional dissemination
Radiotherapy
- Non-metastatic pure germinoma in PR/SD After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy)
- Non-metastatic germinoma in CR After Chemotherapy: 24 Gy (15 fractions) to whole ventricles
- Non-metastatic germinoma plus teratoma (incompletely resected) After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)
干预措施: Carboplatin, Etoposide, Ifosfamide (Drug)
germinoma non-metastatic
Chemotherapy:
• Non-metastatic fully staged germinoma (± teratoma) Two courses (1 and 3) of Etoposide and Carboplatin, alternating with two courses (2 and 4) of Etoposide and Ifosfamide Note: Bifocal germinoma (pineal+suprasellar) are treated as non-metastatic germinoma, if staging shows no additional dissemination
Radiotherapy
- Non-metastatic pure germinoma in PR/SD After Chemotherapy: 24 Gy (15 fractions) to whole ventricles with a 16 Gy (10 fraction) boost to tumour bed (total tumour dose 40 Gy)
- Non-metastatic germinoma in CR After Chemotherapy: 24 Gy (15 fractions) to whole ventricles
- Non-metastatic germinoma plus teratoma (incompletely resected) After Chemotherapy: 24 Gy (15 fractions) to whole ventricles; 30.4 Gy (19 fraction) boost to tumour bed (total tumour dose 54.4 Gy)
干预措施: ventricular irradiation (Radiation)
Non-germinoma non-metastatic standard risk
Chemotherapy:
• Standard risk non-germinomatous malignant GCT Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
干预措施: Cisplatin, etoposide, Ifosfamide (standard) (Drug)
Non-germinoma non-metastatic standard risk
Chemotherapy:
• Standard risk non-germinomatous malignant GCT Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
干预措施: focal irradiation (Radiation)
Non-Germinoma metastatic standard risk
Chemotherapy Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)
干预措施: craniospinal irradiation (Radiation)
Non-Germinoma metastatic standard risk
Chemotherapy Four courses of Etoposide, Cisplatin and Ifosfamide (standard treatment ) Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)
干预措施: Cisplatin, etoposide, Ifosfamide (standard) (Drug)
Non-germinoma non-metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
干预措施: Cisplatin, Etoposide, Ifosfamide (high dose) (Drug)
Non-germinoma non-metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 54 Gy focal radiotherapy in 30 fractions
干预措施: focal irradiation (Radiation)
Non-Germinoma metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)
干预措施: craniospinal irradiation (Radiation)
Non-Germinoma metastatic high risk
Chemotherapy Two courses of standard Etoposide, Cisplatin and Ifosfamide, followed by two dose intensified courses of Etoposide, Cisplatin and Ifosfamide with stem cell support Radiotherapy After Chemotherapy: 30 Gy (20 fractions) to craniospinal axis with 24 Gy (15 fraction) boosts to tumour site and any intracranial metastases (total tumour dose 54 Gy) and 20.8 Gy (13 fraction) boosts to spinal deposits (total dose 50.8 Gy)
干预措施: Cisplatin, Etoposide, Ifosfamide (high dose) (Drug)
结局指标
主要结局
survival
时间窗: 5 years event free survival
Survival rates in respect to applied treatment , according to Kaplan-Meier estimation , 5 years event free survival
次要结局
- short and long term toxicity(until 7 years after start of trial)
- overall survival(7 years after start of trial)