ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00749723
Recruitment Status : Unknown
Verified July 2015 by Gudrun Fleischhack, University Hospital, Essen.
Recruitment status was:  Active, not recruiting
First Posted : September 9, 2008
Last Update Posted : July 8, 2015
Sponsor:
Information provided by (Responsible Party):
Gudrun Fleischhack, University Hospital, Essen

Study Description
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment 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

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)


Study Design
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Study Start Date : February 2006
Actual Primary Completion Date : January 2013
Estimated Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Brain Tumors
U.S. FDA Resources

Arms and Interventions
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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


Outcome Measures
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. P-HIT-REZ 2005 study: two Chemotherapy-arms: overall survival from start of therapy [ Time Frame: 10 years ]
  2. E-HIT-REZ 2005 study: Chemotherapy-arm: progression-free survival from start of therapy [ Time Frame: 10 years ]
  3. E-HIT-REZ 2005 study: Chemotherapy-arm: overall survival from start of therapy [ Time Frame: 10 years ]
  4. E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) [ Time Frame: 10 years ]
  5. Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC) [ Time Frame: 8 years ]
  6. P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms [ Time Frame: 8 years ]

Eligibility Criteria
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   3 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00749723


  Show 54 Study Locations
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
Go to 
Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
German Society of Pediatric Hematology and Oncology  This link exits the ClinicalTrials.gov site
German Children's Cancer Foundation  This link exits the ClinicalTrials.gov site

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
First Posted: September 9, 2008    Key Record Dates
Last Update Posted: July 8, 2015
Last Verified: July 2015

Keywords provided by Gudrun Fleischhack, University Hospital, Essen:
brain tumor
relapse
children
 etoposide
intraventricular
temozolomide

Additional relevant MeSH terms:
Brain Neoplasms
Ependymoma
Medulloblastoma
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
Neuroectodermal Tumors, Primitive
Etoposide phosphate
Temozolomide
Trofosfamide
Carboplatin
Etoposide
Dacarbazine
Thiotepa
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors