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

NCT ID: NCT00749723

Last Updated: 2018-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-01
• Study Completion Date: 2016-01-31

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)

Conditions

Recurrent Brain Tumors; Supratentorial PNETs; Medulloblastomas; Ependymomas

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

carboplatin

Intervention Type: DRUG

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

Intervention Type: DRUG

100mg/m²/d continuously IV on day 1-4 of each 21-28 day cycle. Number of cycles: until disease progression, maximum 4 cycles

thiotepa, carboplatin, etoposide

Intervention Type: DRUG

high dose chemotherapy followed by to autologous stem cell transplantation

autologous stem cell transplantation

Intervention Type: PROCEDURE

autologous stem cell transplantation following HD-chemotherapy

intraventricular etoposide

Intervention Type: DRUG

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

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

temozolomide

Intervention Type: DRUG

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

temozolomide, thiotepa

Intervention Type: DRUG

high dose chemotherapy followed by autologous stem cell transplantation

autologous stem cell transplantation

Intervention Type: PROCEDURE

autologous stem cell transplantation following HD-chemotherapy

intraventricular etoposide

Intervention Type: DRUG

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

3: E-HIT-REZ 2005

Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide

Group Type: EXPERIMENTAL

temozolomide

Intervention Type: DRUG

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

intraventricular etoposide

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intraventricular Etoposide

Phase II, intraventricular chemotherapy with etoposide

Group Type: EXPERIMENTAL

intraventricular etoposide

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

thiotepa, carboplatin, etoposide

high dose chemotherapy followed by to autologous stem cell transplantation

Intervention Type: DRUG

temozolomide, thiotepa

high dose chemotherapy followed by autologous stem cell transplantation

Intervention Type: DRUG

autologous stem cell transplantation

autologous stem cell transplantation following HD-chemotherapy

Intervention Type: PROCEDURE

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Carboplatin IV; etoposide IV; temozolomide orally; thiotepa, carboplatin, etoposide IV, high dose; temozolomide, thiotepa IV; ASCT; etoposide intra-CSF; trofosfamide, etoposide orally

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bonn

OTHER

Sponsor Role: lead

Responsible Party

Gudrun Fleischhack

MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gudrun Fleischhack, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen

Locations

Universitätskinderklinik Aachen

Aachen, , Germany

Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin

Augsburg, , Germany

Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin

Berlin, , Germany

Charité Klinikum Campus Virchow, Kinderklinik

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

Universitätskinderklinik Köln

Cologne, , 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 am Main, , Germany

Universitätskinderklinik Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde

Giessen, , Germany

Universitätskinderklinik Göttingen

Göttingen, , Germany

Universitätskinderklinik Greifswald

Greifswald, , Germany

Martin-Luther-Universität Halle Wittenberg

Halle, , Germany

Universitätskinderklinik Hamburg-Eppendorf

Hamburg, , Germany

Medizinische Hochschule, Zentrum für Kinderheilkunde

Hanover, , 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 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

Nuremberg, , 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, , Germany

Countries

Germany

Related Links

http://www.kinderkrebsinfo.de/

German Society of Pediatric Hematology and Oncology

http://www.kinderkrebsstiftung.de/

German Children's Cancer Foundation

Other Identifiers

BfArM-4030755

Identifier Type: OTHER

Identifier Source: secondary_id

EC-105/05

Identifier Type: OTHER

Identifier Source: secondary_id

DKS 2006.01, 2008.17, 2012.03

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EUDRACT 2005-002618-40

Identifier Type: -

Identifier Source: org_study_id