Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children
- Conditions
- MedulloblastomasEpendymomasSupratentorial PNETsRecurrent Brain Tumors
- Interventions
- Drug: temozolomide, thiotepaProcedure: autologous stem cell transplantation
- Registration Number
- NCT00749723
- Lead Sponsor
- University Hospital, Bonn
- 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)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 174
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
Renal:
- Creatinine no greater than 1.5 times UNL
- No overt renal disease
Hepatic:
- Bilirubin less than 2.5 times UNL
- AST and ALT less than 5 times UNL
- No overt hepatic disease
Pulmonary:
- No overt pulmonary disease
Cardiovascular:
- No overt cardiovascular disease
Other:
- 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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 1: P-HIT-REZ 2005 thiotepa, carboplatin, etoposide 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 1: P-HIT-REZ 2005 autologous stem cell transplantation 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 1: P-HIT-REZ 2005 intraventricular etoposide 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 2: P-HIT-REZ 2005 temozolomide, thiotepa 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 2: P-HIT-REZ 2005 autologous stem cell transplantation 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 2: P-HIT-REZ 2005 intraventricular etoposide 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 3: E-HIT-REZ 2005 temozolomide Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide 3: E-HIT-REZ 2005 intraventricular etoposide Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide Intraventricular Etoposide intraventricular etoposide Phase II, intraventricular chemotherapy with etoposide 1: P-HIT-REZ 2005 trofosfamide, etoposide 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 3: E-HIT-REZ 2005 trofosfamide, etoposide Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide 1: P-HIT-REZ 2005 carboplatin 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 1: P-HIT-REZ 2005 etoposide 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 2: P-HIT-REZ 2005 temozolomide 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
- Primary Outcome Measures
Name Time Method P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course 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 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 6 weeks for each patient (8 years for the whole study population) disease stabilization rate (CR+PR+SD/all patients)
- Secondary Outcome Measures
Name Time Method E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy 10 years progression free and overall survival from start of therapy until PD, last follow up or death, respectively
Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC) 8 years rate of adverse events of CTC°1-4 according to CTCAE v3.0
P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy 10 years progression free and overall survival from start of therapy until PD, last follow up or death, respectively
P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms 8 years rate of adverse events of CTC°3 or CTC°4 according to CTCAE v3.0
E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) 10 years progression free and overall survival from start of therapy until PD, last follow up or death, respectively
Trial Locations
- Locations (54)
Universitätskinderklinik Freiburg
🇩🇪Freiburg, Germany
Universitätskinderklinik Göttingen
🇩🇪Göttingen, Germany
Universitätskinderklinik Heidelberg
🇩🇪Heidelberg, Germany
Universitätskinderklinik Aachen
🇩🇪Aachen, Germany
Universitätskinderklinik Mainz
🇩🇪Mainz, Germany
Universitätskinderklinik Essen
🇩🇪Essen, Germany
Klinikum Bremen-Mitte
🇩🇪Bremen, Germany
Vestische Kinder- und Jugendklinik Datteln
🇩🇪Datteln, Germany
Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin
🇩🇪Dortmund, Germany
Helios Klinikum Erfurt, Zentrum für Kinderheilkunde
🇩🇪Erfurt, Germany
Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde
🇩🇪Gießen, Germany
Universitätskinderklinik Düsseldorf
🇩🇪Düsseldorf, Germany
SLK Kinderklinik Heilbronn
🇩🇪Heilbronn, Germany
Universitätskinderklinik Greifswald
🇩🇪Greifswald, Germany
Klinikum der Wolfgang Goethe Universität, Klinik für Kinderheilkunde
🇩🇪Frankfurt/Main, Germany
Martin-Luther-Universität Halle Wittenberg
🇩🇪Halle/Saale, Germany
Städtisches Krankenhaus, Klinik für Kinder- und Jugendmedizin
🇩🇪Karlsruhe, Germany
Städtisches Klinikum Kemperhof, Klinik für Kinder- und Jugendmedizin
🇩🇪Koblenz, Germany
Universitätskinderklinik Köln
🇩🇪Köln, Germany
Universitätskinderklinik Leipzig
🇩🇪Leipzig, Germany
Universitätskinderklinik Marburg
🇩🇪Marburg, Germany
Klinikum Minden III, Klinik für Kinder-und Jugendheilkunde
🇩🇪Minden, Germany
Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin
🇩🇪Oldenburg, Germany
Universitätskinderklinik Lübeck
🇩🇪Lübeck, Germany
Universitätskinderklinik Mannheim
🇩🇪Mannheim, Germany
Asklepios Klinik Sankt Augustin GmbH
🇩🇪Sankt Augustin, Germany
Univeritätsklinikum Ulm, Abteilung Kinder-und Jugendmedizin
🇩🇪Ulm, Germany
Olgahospital-Pädiatrisches Zentrum
🇩🇪Stuttgart, Germany
Universitätskinderklinik Tübingen
🇩🇪Tübingen, Germany
Otto-von-Guericke-Universität, Zentrum für Kinderheilkunde
🇩🇪Magdeburg, Germany
Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin
🇩🇪Berlin, Germany
Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin
🇩🇪Augsburg, Germany
Charité Klinikum Campus Virchow, Kinderklinik
🇩🇪Berlin, Germany
Universitätskinderklinik Bonn
🇩🇪Bonn, Germany
Städtisches Klinikum Braunschweig, Kinderklinik
🇩🇪Braunschweig, Germany
Klinik ür Kinder- und Jugendmedizin in Bethel
🇩🇪Bielefeld, Germany
Carl-Thiele-Klinikum Cottbus, Zentrum für Kinderheilkunde
🇩🇪Cottbus, Germany
Universitätsklinikum Dresden, Kinderklinik
🇩🇪Dresden, Germany
Universitätskinderklinik Erlangen
🇩🇪Erlangen, Germany
Klinikum Duisburg, Klinik für Kinder-und Jugendmedizin
🇩🇪Duisburg, Germany
Medizinische Hochschule, Zentrum für Kinderheilkunde
🇩🇪Hannover, Germany
Universitätskinderklinik Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Gemeinschaftskrankenhaus Herdecke, Kinderklinik
🇩🇪Herdecke, Germany
Universitätskinderklinik
🇩🇪Homburg/Saar, Germany
UKSH, Campus Kiel, Klinik für Allg. Pädiatrie
🇩🇪Kiel, Germany
Klinikum Kassel, Kinderklinik
🇩🇪Kassel, Germany
Universitätskinderklinik Rostock
🇩🇪Rostock, Germany
Universitäts-Kinderklinik
🇩🇪Regensburg, Germany
Universitätskinderklinik Würzburg
🇩🇪Würzburg, Germany
Cnopf'sche Kinderklinik
🇩🇪Nürnberg, Germany
Dr. von Haunersches Kinderspital
🇩🇪München, Germany
Städtisches Krankenhaus München-Schwabing, Kinderklinik der TU München
🇩🇪München, Germany
Friedrich Schiller Universität, Klinik für Kinder-und Jugendmedizin
🇩🇪Jena, Germany
Universitätskinderklinik Münster
🇩🇪Münster, Germany