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
Overview
- Phase
- Phase 2
- Intervention
- carboplatin
- Conditions
- Recurrent Brain Tumors
- Sponsor
- University Hospital, Bonn
- Enrollment
- 174
- Locations
- 54
- Primary Endpoint
- P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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)
Investigators
Gudrun Fleischhack
MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
University Hospital, Essen
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
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
Intervention: carboplatin
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
Intervention: etoposide
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
Intervention: thiotepa, carboplatin, etoposide
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
Intervention: autologous stem cell transplantation
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
Intervention: intraventricular etoposide
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
Intervention: trofosfamide, etoposide
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
Intervention: temozolomide
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
Intervention: temozolomide, thiotepa
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
Intervention: autologous stem cell transplantation
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
Intervention: intraventricular etoposide
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
Intervention: temozolomide
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
Intervention: intraventricular etoposide
3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
Intervention: trofosfamide, etoposide
Intraventricular Etoposide
Phase II, intraventricular chemotherapy with etoposide
Intervention: intraventricular etoposide
Outcomes
Primary Outcomes
P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course
Time Frame: 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
Time Frame: 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
Time Frame: 6 weeks for each patient (8 years for the whole study population)
disease stabilization rate (CR+PR+SD/all patients)
Secondary Outcomes
- 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)