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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 : Completed
First Posted : September 9, 2008
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Gudrun Fleischhack, University Hospital, Essen

Tracking Information
First Submitted Date  ICMJE September 5, 2008
First Posted Date  ICMJE September 9, 2008
Last Update Posted Date July 20, 2018
Study Start Date  ICMJE February 1, 2006
Actual Primary Completion Date January 31, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course [ Time Frame: 4 months for each patient (8 years for the whole study population) ]
    determination of objective repsonse rate (CR+PR)
  • 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 for each patient (8 years for the whole study population) ]
    determination of objective repsonse rate (CR+PR/all patients)
  • Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide [ Time Frame: 6 weeks for each patient (8 years for the whole study population) ]
    disease stabilization rate (CR+PR+SD/all patients)
Original Primary Outcome Measures  ICMJE
 (submitted: September 5, 2008)
  • 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 ]
  • 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 ]
  • Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide [ Time Frame: 6 weeks ]
Change History Complete list of historical versions of study NCT00749723 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy [ Time Frame: 10 years ]
    progression free and overall survival from start of therapy until PD, last follow up or death, respectively
  • P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms [ Time Frame: 8 years ]
    rate of adverse events of CTC°3 or CTC°4 according to CTCAE v3.0
  • E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy [ Time Frame: 10 years ]
    progression free and overall survival from start of therapy until PD, last follow up or death, respectively
  • E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) [ Time Frame: 10 years ]
    progression free and overall survival from start of therapy until PD, last follow up or death, respectively
  • Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC) [ Time Frame: 8 years ]
    rate of adverse events of CTC°1-4 according to CTCAE v3.0
Original Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2008)
  • 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 ]
  • 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 ]
  • P-HIT-REZ 2005 study: Chemotherapy-arms: toxicity rate (CTC) in both arms [ Time Frame: 8 years ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: progression-free survival from start of therapy [ Time Frame: 10 years ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: overall survival from start of therapy [ Time Frame: 10 years ]
  • E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) [ Time Frame: 10 years ]
  • Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC) [ Time Frame: 6 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children
Official Title  ICMJE 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
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)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Brain Tumors
  • Supratentorial PNETs
  • Medulloblastomas
  • Ependymomas
Intervention  ICMJE
  • 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
    Other Name: Carboplatin IV
  • 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
    Other Name: etoposide IV
  • 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
    Other Name: temozolomide orally
  • Drug: thiotepa, carboplatin, etoposide
    high dose chemotherapy followed by to autologous stem cell transplantation
    Other Name: thiotepa, carboplatin, etoposide IV, high dose
  • Drug: temozolomide, thiotepa
    high dose chemotherapy followed by autologous stem cell transplantation
    Other Name: temozolomide, thiotepa IV
  • Procedure: autologous stem cell transplantation
    autologous stem cell transplantation following HD-chemotherapy
    Other Name: ASCT
  • Drug: 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
    Other Name: etoposide intra-CSF
  • 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
    Other Name: trofosfamide, etoposide orally
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: carboplatin
    • Drug: etoposide
    • Drug: thiotepa, carboplatin, etoposide
    • Procedure: autologous stem cell transplantation
    • Drug: intraventricular etoposide
    • Drug: trofosfamide, etoposide
  • Experimental: 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
    Interventions:
    • Drug: temozolomide
    • Drug: temozolomide, thiotepa
    • Procedure: autologous stem cell transplantation
    • Drug: intraventricular etoposide
  • Experimental: 3: E-HIT-REZ 2005
    Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
    Interventions:
    • Drug: temozolomide
    • Drug: intraventricular etoposide
    • Drug: trofosfamide, etoposide
  • Experimental: Intraventricular Etoposide
    Phase II, intraventricular chemotherapy with etoposide
    Intervention: Drug: intraventricular etoposide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2018)
174
Original Estimated Enrollment  ICMJE
 (submitted: September 5, 2008)
200
Actual Study Completion Date  ICMJE January 31, 2016
Actual Primary Completion Date January 31, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Months to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00749723
Other Study ID Numbers  ICMJE EUDRACT 2005-002618-40
BfArM-4030755 ( Other Identifier: Federal Institute for Drugs and Medical Devices (BfArM) )
EC-105/05 ( Other Identifier: Leading Ethic Committee University Hospital of Bonn )
DKS 2006.01, 2008.17, 2012.03 ( Other Grant/Funding Number: German Children Cancer Foundation )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gudrun Fleischhack, University Hospital, Essen
Study Sponsor  ICMJE University Hospital, Bonn
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gudrun Fleischhack, MD Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen
PRS Account University Hospital, Bonn
Verification Date July 2018

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