HIT-REZ 2005

Title Therapy-Optimization Trial and Phase II Study for the Treatment of Relapsed or Refractory Primitive Neuroectodermal Brain Tumors and Ependymomas in Children and Adolescents

Version 6: 10.03.2011, incl. 3. Amendment

Disease Patients with refractory or recurrent brain tumors (medulloblastomas, supratentorial PNETs, ependymomas WHO grade II and III)
Type Therapy-Optimazation Trial and Phase-II-Study
Problem / Objectives

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.

1. P-HIT-REZ 2005:

Aim of this study is the evaluation of the efficacy of the systemic chemotherapy with carboplatin/etoposide i.v. versus oral chemotherapy with temozolomide.
Study-arms:

  1. intravenous chemotherapy with carboplatin/etoposide
  2. oral chemotherapy with temozolomide
  3. Documentation-arm: only for patients, who do not give written consense to a chemotherapy or patients with a medical condition, which does not allow intensive chemotherapy.

Primary Outcome Measures: Evaluation of progression-free survival, overall-survival and response to intravenous and oral chemotherapy.

2. E-HIT-REZ 2005 Phase II-Temozolomide, Recruitment from 01.06.2008:

The aim of the study is the evaluation of the response rate to the 60-days oral chemotherapy with temozolomide on behalf of neuroradiological, cytological (CSF) and neurological findings.
Study-arms:

  1. oral chemotherapy with temozolomide
  2. Documentation-arm: only for patients, who do not give written consense to a chemotherapy or patients with a medical condition, which does not allow intensive chemotherapy.

Secondary objective: Evaluation of the progression-free survival, the overall-survival and the response to oral chemotherapy with temozomolide.

3. Phase-II-study: etoposide intraventricular

Aim of this study is the evaluation of the efficacy of intraventricular etoposide in patients with refractory or relapsed disease and neoplastic meningitis in PNETs and ependymomas with subarachnoid tumor manifestation. Only patients without progress in the subarachnoid desease after the 5-weeks window-therapy should continue the intraventicular therapy with etoposide during the systemic chemotherapy.

Primary Objetives: Evaluation of response rate to the 5-week intraventricular therapy
6 weeks after start of therapy with etoposide on behalf of clinical and radiological findings (MRT) and cytological findings into the cerebrospinal fluid.

Therapy / Study arms

The study is devided in the following parts

  1. P-HIT-REZ 2005: a trial for the treatment of relapsed PNETs (medulloblastomas,supratentorial PNETs)
  2. E-HIT-REZ 2005: a trial for the treatment of relapsed ependymomas (Phase II-Study with temozolomide)
  3. Phase-II-Study: intraventricular therapy with etoposide in neoplastic meningitis in relapsed PNETs and ependymomas with subarachnoid tumor manifestation (window study)

Design of the parts

  1. P-HIT-REZ 2005: Multicenter, non blinded, non randomized, prospective, multiarm observation study
  2. E-HIT-REZ 2005: Multicenter, non blinded, non randomized, prospective, multiarm phase-II efficacy study
  3. Phase-II-study etoposide intraventricular: Multicenter, non blinded, non randomized, prospective, single arm efficacy study

Concomitant studies

  • Pharmacokinetic screening of Etoposide in the cerebrospinal fluid
  • Leucoencephalopathy after multimodal therapy
  • Neuropsychologic testing over the course of time
  • Live situation and health related quality of live in children and adolescents with a relapsed brain tumour
  • Clinical relevance of molecular genetic changes in CNS PNET and Ependymoma
  • Relevance of somatostatin receptor scintigraphy (Octreoscan) in relapsed CNS PNETs
Inclusion Criteria

For all arms:

  • Histologically confirmed Medulloblastoma, cerebral PNET or Ependymoma
  • Refractory or progressive desease of the primary tumour or relapsed disease
  • Age: 3 Months to 30 Years
  • Cranial and spinal MRI, examination of the spinal and evt. cranial cerebrospinal fluid for tumour-cells within two weeks before start of study therapy
  • Measurable disease by MRI or detection of tumor cells in cerebrospinal fluid Patients characteristics
Status Start of the Study: 01.02.2006
End of recruitment: 31.01.2013
End of the study P-HIT-REZ: 31.01.2016
End of the study E-HIT-REZ: 31.01.2016
End of the Phase II-Study Etposide intraventricular: 31.03.2014
EudraCT 2005-002618-40
Entry Study Register
Principal Investigator Prof. Dr. med. Gudrun Fleischhack
E-Mail mailto:gudrun.fleischack@uk-essen.de
Contact

Principal Investigator

Prof. Dr. med. Gudrun Fleischhack
Universitätsklinikum Essen
Zentrum für Kinder- und Jugendmedizin, Klinik für Kinderheilkunde III
Hufelandstr. 55
45147 Essen
Telefon +49 (201) 723-82255/-3350
Fax +49 (201) 723-5608
gudrun.fleischhack@uk-essen.de

Assistance

Prof. Dr. med. Gudrun Fleischhack
Universitätsklinikum Essen
Zentrum für Kinder- und Jugendmedizin, Klinik für Kinderheilkunde III
Hufelandstr. 55
45147 Essen
Telefon +49 (201) 723-82255/-3350
Fax +49 (201) 723-5608
gudrun.fleischhack@uk-essen.de

Study documentation / Monitoring

Prof. Dr. med. Gudrun Fleischhack
Universitätsklinikum Essen
Zentrum für Kinder- und Jugendmedizin, Klinik für Kinderheilkunde III
Hufelandstr. 55
45147 Essen
Telefon +49 (201) 723-82255/-3350
Fax +49 (201) 723-5608
gudrun.fleischhack@uk-essen.de

Radiooncological Questions

Prof. Dr. med. Gudrun Fleischhack
Universitätsklinikum Essen
Zentrum für Kinder- und Jugendmedizin, Klinik für Kinderheilkunde III
Hufelandstr. 55
45147 Essen
Telefon +49 (201) 723-82255/-3350
Fax +49 (201) 723-5608
gudrun.fleischhack@uk-essen.de

Participants 54 centers / participating hospitals in germany with positive ehical votum
Weitere Informationen Clinical Trial Number: EUDRACT 2005-002618-40
Deutsche Krebsgesellschaft: 05-05
Vorlage-Nr. BfArM: 4030755
Federführende Ethikkommission Bonn: 105/05
NCT-Register: NCT 00749723
Projekt-Nr. Deutsche Kinderkrebsstiftung DKS 2006.01/2008.17
Documents
Link(s) HIT-trial literature
Sponsoring The study HIT-REZ 2005 is supported within the Network HIT by the Deutsche Kinderkrebsstiftung. The study has the certificate A of the Deutschen Krebsgesellschaft e. V. .