Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children

Ependymomas Clinical Trial

— HIT-REZ-2005  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00749723
• Other study ID #: EUDRACT 2005-002618-40
• Secondary ID: BfArM-4030755EC-
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 1, 2006
• Est. completion date: January 31, 2016

Study information

• Verified date: July 2018
• Source: University Hospital, Bonn
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: January 31, 2016
• Est. primary completion date: January 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Ependymoma
• Ependymomas
• Medulloblastoma
• Medulloblastomas
• Recurrent Brain Tumors
• Supratentorial PNETs

Intervention

Drug:
• carboplatin
200 mg/m²/d continuously IV on day 1-4 of each 21-28-day-cycle. Number of cycles: until disease progression, maximum 4 cycles
• etoposide
100mg/m²/d continuously IV on day 1-4 of each 21-28 day cycle. Number of cycles: until disease progression, maximum 4 cycles
• temozolomide
150mg/m²/d p.o. on day 1-5 of a 21-28-day-cycle. Number of cycles: until progression or maximum up to 2 years
• thiotepa, carboplatin, etoposide
high dose chemotherapy followed by to autologous stem cell transplantation
• temozolomide, thiotepa
high dose chemotherapy followed by autologous stem cell transplantation

Procedure:
• autologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy

Drug:
• intraventricular etoposide
prior to systemic chemotherapy as single agent in patients with neoplastic meningitis, in addition to systemic chemotherapy if proven effective in phase II study, intraventricularly age-dependent daily dose (>3m to <3y 0.7 mg; >3y 1.0 mg) for 5 days every 2 two 4 weeks. Number of cycles: at least 3 courses, maximum up to 2 years
• trofosfamide, etoposide
maintenance therapy: trofosfamide and etoposide: 100 mg/m²/d and 25 mg/m²/d, respectively, for 21 days every 4 weeks. Number of cycles: until progression or maximum up to 2 years

Locations

Country	Name	City	State
Germany	Universitätskinderklinik Aachen	Aachen
Germany	Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin	Augsburg
Germany	Charité Klinikum Campus Virchow, Kinderklinik	Berlin
Germany	Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin	Berlin
Germany	Klinik ür Kinder- und Jugendmedizin in Bethel	Bielefeld
Germany	Universitätskinderklinik Bonn	Bonn
Germany	Städtisches Klinikum Braunschweig, Kinderklinik	Braunschweig
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Carl-Thiele-Klinikum Cottbus, Zentrum für Kinderheilkunde	Cottbus
Germany	Vestische Kinder- und Jugendklinik Datteln	Datteln
Germany	Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin	Dortmund
Germany	Universitätsklinikum Dresden, Kinderklinik	Dresden
Germany	Klinikum Duisburg, Klinik für Kinder-und Jugendmedizin	Duisburg
Germany	Universitätskinderklinik Düsseldorf	Düsseldorf
Germany	Helios Klinikum Erfurt, Zentrum für Kinderheilkunde	Erfurt
Germany	Universitätskinderklinik Erlangen	Erlangen
Germany	Universitätskinderklinik Essen	Essen
Germany	Klinikum der Wolfgang Goethe Universität, Klinik für Kinderheilkunde	Frankfurt/Main
Germany	Universitätskinderklinik Freiburg	Freiburg
Germany	Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde	Gießen
Germany	Universitätskinderklinik Göttingen	Göttingen
Germany	Universitätskinderklinik Greifswald	Greifswald
Germany	Martin-Luther-Universität Halle Wittenberg	Halle/Saale
Germany	Universitätskinderklinik Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule, Zentrum für Kinderheilkunde	Hannover
Germany	Universitätskinderklinik Heidelberg	Heidelberg
Germany	SLK Kinderklinik Heilbronn	Heilbronn
Germany	Gemeinschaftskrankenhaus Herdecke, Kinderklinik	Herdecke
Germany	Universitätskinderklinik	Homburg/Saar
Germany	Friedrich Schiller Universität, Klinik für Kinder-und Jugendmedizin	Jena
Germany	Städtisches Krankenhaus, Klinik für Kinder- und Jugendmedizin	Karlsruhe
Germany	Klinikum Kassel, Kinderklinik	Kassel
Germany	UKSH, Campus Kiel, Klinik für Allg. Pädiatrie	Kiel
Germany	Städtisches Klinikum Kemperhof, Klinik für Kinder- und Jugendmedizin	Koblenz
Germany	Universitätskinderklinik Köln	Köln
Germany	Universitätskinderklinik Leipzig	Leipzig
Germany	Universitätskinderklinik Lübeck	Lübeck
Germany	Otto-von-Guericke-Universität, Zentrum für Kinderheilkunde	Magdeburg
Germany	Universitätskinderklinik Mainz	Mainz
Germany	Universitätskinderklinik Mannheim	Mannheim
Germany	Universitätskinderklinik Marburg	Marburg
Germany	Klinikum Minden III, Klinik für Kinder-und Jugendheilkunde	Minden
Germany	Dr. von Haunersches Kinderspital	München
Germany	Städtisches Krankenhaus München-Schwabing, Kinderklinik der TU München	München
Germany	Universitätskinderklinik Münster	Münster
Germany	Cnopf'sche Kinderklinik	Nürnberg
Germany	Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin	Oldenburg
Germany	Universitäts-Kinderklinik	Regensburg
Germany	Universitätskinderklinik Rostock	Rostock
Germany	Asklepios Klinik Sankt Augustin GmbH	Sankt Augustin
Germany	Olgahospital-Pädiatrisches Zentrum	Stuttgart
Germany	Universitätskinderklinik Tübingen	Tübingen
Germany	Univeritätsklinikum Ulm, Abteilung Kinder-und Jugendmedizin	Ulm
Germany	Universitätskinderklinik Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course	determination of objective repsonse rate (CR+PR)	4 months for each patient (8 years for the whole study population)
Primary	E-HIT-REZ 2005 study (Phase II Study "Oral chemotherapy with temozolomide"): Evaluation of response rate to the 60-days oral chemotherapy with temozolomide	determination of objective repsonse rate (CR+PR/all patients)	2 months for each patient (8 years for the whole study population)
Primary	Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide	disease stabilization rate (CR+PR+SD/all patients)	6 weeks for each patient (8 years for the whole study population)
Secondary	P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy	progression free and overall survival from start of therapy until PD, last follow up or death, respectively	10 years
Secondary	P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms	rate of adverse events of CTC°3 or CTC°4 according to CTCAE v3.0	8 years
Secondary	E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy	progression free and overall survival from start of therapy until PD, last follow up or death, respectively	10 years
Secondary	E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC)	progression free and overall survival from start of therapy until PD, last follow up or death, respectively	10 years
Secondary	Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC)	rate of adverse events of CTC°1-4 according to CTCAE v3.0	8 years

External Links

•   German Children's Cancer Foundation
•   German Society of Pediatric Hematology and Oncology