Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children (HIT-REZ-2005)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gudrun Fleischhack, University Hospital, Essen
ClinicalTrials.gov Identifier:
NCT00749723
First received: September 5, 2008
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Brain Tumors
Supratentorial PNETs
Medulloblastomas
Ependymomas
Drug: carboplatin
Drug: etoposide
Drug: temozolomide
Drug: thiotepa, carboplatin, etoposide
Drug: temozolomide, thiotepa
Procedure: autologous stem cell transplantation
Drug: trofosfamide/etoposide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: progression-free survival from therapy start and response evaluation after the fourth therapy course [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: overall survival from start of therapy [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: progression-free survival from start of therapy [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: overall survival from start of therapy [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  • Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC) [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 160
Study Start Date: February 2006
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide
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
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
Drug: thiotepa, carboplatin, etoposide
HD-chemotherapy prior to stem cell transplantation
Procedure: autologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy
Drug: 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
Drug: trofosfamide/etoposide
maintenance therapy: trofosfamide/etoposide: 25 and 100 mg/m²/d for 21 days every 4 weeks. Number of cycles: until progression or maximum up to 2 years
Experimental: 2: P-HIT-REZ 2005
oral chemotherapy with temozolomide
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
Drug: temozolomide, thiotepa
HD-chemotherapy prior to autologous stem cell transplantation
Procedure: autologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy
Drug: 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
Experimental: 3: E-HIT-REZ 2005
Phase II
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
Drug: 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
Drug: trofosfamide/etoposide
maintenance therapy: trofosfamide/etoposide: 25 and 100 mg/m²/d for 21 days every 4 weeks. Number of cycles: until progression or maximum up to 2 years
Experimental: Intravent. Etoposide
Phase II
Drug: 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

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

Ages Eligible for Study:   3 Months to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749723

  Hide Study Locations
Locations
Germany
Universitätskinderklinik Aachen
Aachen, Germany, 52074
Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin
Augsburg, Germany, 86156
Charité Klinikum Campus Virchow, Kinderklinik
Berlin, Germany, 13353
Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin
Berlin, Germany, 13125
Klinik ür Kinder- und Jugendmedizin in Bethel
Bielefeld, Germany, 33617
Universitätskinderklinik Bonn
Bonn, Germany, 53113
Städtisches Klinikum Braunschweig, Kinderklinik
Braunschweig, Germany, 38118
Klinikum Bremen-Mitte
Bremen, Germany, 28177
Carl-Thiele-Klinikum Cottbus, Zentrum für Kinderheilkunde
Cottbus, Germany, 03048
Vestische Kinder- und Jugendklinik Datteln
Datteln, Germany, 45711
Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin
Dortmund, Germany, 44137
Universitätsklinikum Dresden, Kinderklinik
Dresden, Germany, 01307
Klinikum Duisburg, Klinik für Kinder-und Jugendmedizin
Duisburg, Germany, 47055
Universitätskinderklinik Düsseldorf
Düsseldorf, Germany, 40225
Helios Klinikum Erfurt, Zentrum für Kinderheilkunde
Erfurt, Germany, 99089
Universitätskinderklinik Erlangen
Erlangen, Germany, 91054
Universitätskinderklinik Essen
Essen, Germany, 45122
Klinikum der Wolfgang Goethe Universität, Klinik für Kinderheilkunde
Frankfurt/Main, Germany, 60590
Universitätskinderklinik Freiburg
Freiburg, Germany, 79106
Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde
Gießen, Germany, 35385
Universitätskinderklinik Greifswald
Greifswald, Germany, 17475
Universitätskinderklinik Göttingen
Göttingen, Germany, 37075
Martin-Luther-Universität Halle Wittenberg
Halle/Saale, Germany, 06120
Universitätskinderklinik Hamburg-Eppendorf
Hamburg, Germany, 20246
Medizinische Hochschule, Zentrum für Kinderheilkunde
Hannover, Germany, 30625
Universitätskinderklinik Heidelberg
Heidelberg, Germany, 69120
SLK Kinderklinik Heilbronn
Heilbronn, Germany, 74078
Gemeinschaftskrankenhaus Herdecke, Kinderklinik
Herdecke, Germany, 58313
Universitätskinderklinik
Homburg/Saar, Germany, 66421
Friedrich Schiller Universität, Klinik für Kinder-und Jugendmedizin
Jena, Germany, 07745
Städtisches Krankenhaus, Klinik für Kinder- und Jugendmedizin
Karlsruhe, Germany, 76133
Klinikum Kassel, Kinderklinik
Kassel, Germany, 34125
UKSH, Campus Kiel, Klinik für Allg. Pädiatrie
Kiel, Germany, 24105
Städtisches Klinikum Kemperhof, Klinik für Kinder- und Jugendmedizin
Koblenz, Germany, 56073
Universitätskinderklinik Köln
Köln, Germany, 50924
Universitätskinderklinik Leipzig
Leipzig, Germany, 04317
Universitätskinderklinik Lübeck
Lübeck, Germany, 23538
Otto-von-Guericke-Universität, Zentrum für Kinderheilkunde
Magdeburg, Germany, 39120
Universitätskinderklinik Mainz
Mainz, Germany, 55131
Universitätskinderklinik Mannheim
Mannheim, Germany, 68167
Universitätskinderklinik Marburg
Marburg, Germany, 35043
Klinikum Minden III, Klinik für Kinder-und Jugendheilkunde
Minden, Germany, 32432
Städtisches Krankenhaus München-Schwabing, Kinderklinik der TU München
München, Germany, 80804
Dr. von Haunersches Kinderspital
München, Germany, 80337
Universitätskinderklinik Münster
Münster, Germany, 48129
Cnopf'sche Kinderklinik
Nürnberg, Germany, 90419
Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin
Oldenburg, Germany, 26131
Universitäts-Kinderklinik
Regensburg, Germany, 93042
Universitätskinderklinik Rostock
Rostock, Germany, 18057
Asklepios Klinik St. Augustin GmbH
St. Augustin, Germany, 53757
Olgahospital-Pädiatrisches Zentrum
Stuttgart, Germany, 70176
Universitätskinderklinik Tübingen
Tübingen, Germany, 72076
Univeritätsklinikum Ulm, Abteilung Kinder-und Jugendmedizin
Ulm, Germany, 89075
Universitätskinderklinik Würzburg
Würzburg, Germany, 97080
Sponsors and Collaborators
University Hospital, Bonn
Investigators
Principal Investigator: Gudrun Fleischhack, MD Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
  More Information

Additional Information:
No publications provided

Responsible Party: Gudrun Fleischhack, MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen, University Hospital, Essen
ClinicalTrials.gov Identifier: NCT00749723     History of Changes
Other Study ID Numbers: EUDRACT 2005-002618-40, BfArM-4030755, EC-105/05, DKS 2006.01, DK 2008.17
Study First Received: September 5, 2008
Last Updated: April 25, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital, Bonn:
brain tumor
relapse
children
etoposide
intraventricular
temozolomide

Additional relevant MeSH terms:
Brain Neoplasms
Ependymoma
Medulloblastoma
Neuroectodermal Tumors, Primitive
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide
Etoposide phosphate
Temozolomide
Trofosfamide
Thiotepa
Dacarbazine
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 24, 2014