Clinical trial NCT00749723: Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Recurrent Brain Tumors
Supratentorial PNETs
Medulloblastomas
Ependymomas
Keywords: brain tumor
relapse
children
etoposide
intraventricular
temozolomide
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2008-09-09
Enrollment: 174
Sex: ALL
Minimum age (years): 3
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)

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

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

Primary outcomes:
measure: P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course
timeFrame: 4 months for each patient (8 years for the whole study population)
measure: E-HIT-REZ 2005 study (Phase II Study "Oral chemotherapy with temozolomide"): Evaluation of response rate to the 60-days oral chemotherapy with temozolomide
timeFrame: 2 months for each patient (8 years for the whole study population)
measure: Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide
timeFrame: 6 weeks for each patient (8 years for the whole study population)
Secondary outcomes:
measure: P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy
timeFrame: 10 years
measure: P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms
timeFrame: 8 years
measure: E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy
timeFrame: 10 years
measure: E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC)
timeFrame: 10 years
measure: Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC)
timeFrame: 8 years
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätskinderklinik Aachen
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin
city: Berlin
country: Germany
facility: Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin
city: Berlin
country: Germany
facility: Charité Klinikum Campus Virchow, Kinderklinik
city: Bielefeld
country: Germany
facility: Klinik ür Kinder- und Jugendmedizin in Bethel
city: Bonn
country: Germany
facility: Universitätskinderklinik Bonn
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig, Kinderklinik
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Cottbus
country: Germany
facility: Carl-Thiele-Klinikum Cottbus, Zentrum für Kinderheilkunde
city: Datteln
country: Germany
facility: Vestische Kinder- und Jugendklinik Datteln
city: Dortmund
country: Germany
facility: Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden, Kinderklinik
city: Duisburg
country: Germany
facility: Klinikum Duisburg, Klinik für Kinder-und Jugendmedizin
city: Düsseldorf
country: Germany
facility: Universitätskinderklinik Düsseldorf
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt, Zentrum für Kinderheilkunde
city: Erlangen
country: Germany
facility: Universitätskinderklinik Erlangen
city: Essen
country: Germany
facility: Universitätskinderklinik Essen
city: Frankfurt/Main
country: Germany
facility: Klinikum der Wolfgang Goethe Universität, Klinik für Kinderheilkunde
city: Freiburg
country: Germany
facility: Universitätskinderklinik Freiburg
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde
city: Greifswald
country: Germany
facility: Universitätskinderklinik Greifswald
city: Göttingen
country: Germany
facility: Universitätskinderklinik Göttingen
city: Halle/Saale
country: Germany
facility: Martin-Luther-Universität Halle Wittenberg
city: Hamburg
country: Germany
facility: Universitätskinderklinik Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule, Zentrum für Kinderheilkunde
city: Heidelberg
country: Germany
facility: Universitätskinderklinik Heidelberg
city: Heilbronn
country: Germany
facility: SLK Kinderklinik Heilbronn
city: Herdecke
country: Germany
facility: Gemeinschaftskrankenhaus Herdecke, Kinderklinik
city: Homburg/Saar
country: Germany
facility: Universitätskinderklinik
city: Jena
country: Germany
facility: Friedrich Schiller Universität, Klinik für Kinder-und Jugendmedizin
city: Karlsruhe
country: Germany
facility: Städtisches Krankenhaus, Klinik für Kinder- und Jugendmedizin
city: Kassel
country: Germany
facility: Klinikum Kassel, Kinderklinik
city: Kiel
country: Germany
facility: UKSH, Campus Kiel, Klinik für Allg. Pädiatrie
city: Koblenz
country: Germany
facility: Städtisches Klinikum Kemperhof, Klinik für Kinder- und Jugendmedizin
city: Köln
country: Germany
facility: Universitätskinderklinik Köln
city: Leipzig
country: Germany
facility: Universitätskinderklinik Leipzig
city: Lübeck
country: Germany
facility: Universitätskinderklinik Lübeck
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-Universität, Zentrum für Kinderheilkunde
city: Mainz
country: Germany
facility: Universitätskinderklinik Mainz
city: Mannheim
country: Germany
facility: Universitätskinderklinik Mannheim
city: Marburg
country: Germany
facility: Universitätskinderklinik Marburg
city: Minden
country: Germany
facility: Klinikum Minden III, Klinik für Kinder-und Jugendheilkunde
city: München
country: Germany
facility: Dr. von Haunersches Kinderspital
city: München
country: Germany
facility: Städtisches Krankenhaus München-Schwabing, Kinderklinik der TU München
city: Münster
country: Germany
facility: Universitätskinderklinik Münster
city: Nürnberg
country: Germany
facility: Cnopf'sche Kinderklinik
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin
city: Regensburg
country: Germany
facility: Universitäts-Kinderklinik
city: Rostock
country: Germany
facility: Universitätskinderklinik Rostock
city: Sankt Augustin
country: Germany
facility: Asklepios Klinik Sankt Augustin GmbH
city: Stuttgart
country: Germany
facility: Olgahospital-Pädiatrisches Zentrum
city: Tübingen
country: Germany
facility: Universitätskinderklinik Tübingen
city: Ulm
country: Germany
facility: Univeritätsklinikum Ulm, Abteilung Kinder-und Jugendmedizin
city: Würzburg
country: Germany
facility: Universitätskinderklinik Würzburg
Study officials:
affiliation: Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
name: Gudrun Fleischhack, MD
role: PRINCIPAL_INVESTIGATOR
References: