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

September 5, 2008
April 25, 2013
February 2006
January 2013   (final data collection date for primary outcome measure)
  • 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 ]
  • P-HIT-REZ 2005 study: Evaluation of progression-free survival from randomisation in both chemotherapy-arms (randomisation-arms: intravenous chemotherapy with carboplatin/etoposide vs. oral chemotherapy with temozolomide) [ Time Frame: 8 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 ]
Complete list of historical versions of study NCT00749723 on ClinicalTrials.gov Archive Site
  • 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 ]
  • P-HIT-REZ 2005 study: Chemotherapy-arms: overall survival from randomisation, therapy start and response evaluation after the fourth therapy course [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]
  • P-HIT-REZ 2005 study: Chemotherapy-arms: progression-free survival from therapy start and response evaluation after the fourth therapy course [ Time Frame: 8 years ] [ Designated as safety issue: No ]
  • P-HIT-REZ 2005 study: Chemotherapy-arms: toxicity rate (CTC) in both arms [ Time Frame: 8 years ] [ Designated as safety issue: Yes ]
  • 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: 6 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children
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

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.

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)

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Brain Tumors
  • Supratentorial PNETs
  • Medulloblastomas
  • Ependymomas
  • 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: 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: thiotepa, carboplatin, etoposide
    HD-chemotherapy prior to stem cell transplantation
  • 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
  • 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: 1: P-HIT-REZ 2005
    intravenous chemotherapy with carboplatin/etoposide
    Interventions:
    • Drug: carboplatin
    • Drug: etoposide
    • Drug: thiotepa, carboplatin, etoposide
    • Procedure: autologous stem cell transplantation
    • Drug: etoposide
    • Drug: trofosfamide/etoposide
  • Experimental: 2: P-HIT-REZ 2005
    oral chemotherapy with temozolomide
    Interventions:
    • Drug: temozolomide
    • Drug: temozolomide, thiotepa
    • Procedure: autologous stem cell transplantation
    • Drug: etoposide
  • Experimental: 3: E-HIT-REZ 2005
    Phase II
    Interventions:
    • Drug: temozolomide
    • Drug: etoposide
    • Drug: trofosfamide/etoposide
  • Experimental: Intravent. Etoposide
    Phase II
    Intervention: Drug: etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
160
January 2016
January 2013   (final data collection date for primary outcome measure)

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
Both
3 Months to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00749723
EUDRACT 2005-002618-40, BfArM-4030755, EC-105/05, DKS 2006.01, DK 2008.17
Yes
Gudrun Fleischhack, University Hospital, Essen
University Hospital, Bonn
Not Provided
Principal Investigator: Gudrun Fleischhack, MD Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
University Hospital, Bonn
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP