Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children (HIT-REZ-2005)
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| ClinicalTrials.gov Identifier: NCT00749723 |
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Recruitment Status :
Completed
First Posted : September 9, 2008
Last Update Posted : July 20, 2018
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Sponsor:
University Hospital, Bonn
Information provided by (Responsible Party):
Gudrun Fleischhack, University Hospital, Essen
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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: intraventricular etoposide Drug: trofosfamide, etoposide | Phase 2 Phase 3 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 174 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 1, 2006 |
| Actual Primary Completion Date : | January 31, 2015 |
| Actual Study Completion Date : | January 31, 2016 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Brain Tumors
| Arm | Intervention/treatment |
|---|---|
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Experimental: 1: P-HIT-REZ 2005
intravenous chemotherapy with carboplatin/etoposide,followed by
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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: thiotepa, carboplatin, etoposide high dose chemotherapy followed by to autologous stem cell transplantation
Other Name: thiotepa, carboplatin, etoposide IV, high dose 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 |
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Experimental: 2: P-HIT-REZ 2005
oral chemotherapy with temozolomide, followed by
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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: 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 |
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Experimental: 3: E-HIT-REZ 2005
Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide
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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: 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 |
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Experimental: Intraventricular Etoposide
Phase II, intraventricular chemotherapy with etoposide
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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 |
Primary Outcome Measures :
- 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)
Secondary Outcome Measures :
- 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
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| 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
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
Locations
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 |
Additional Information:
| Responsible Party: | Gudrun Fleischhack, MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen, University Hospital, Essen |
| ClinicalTrials.gov Identifier: | NCT00749723 |
| Other Study ID Numbers: |
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 ) |
| First Posted: | September 9, 2008 Key Record Dates |
| Last Update Posted: | July 20, 2018 |
| Last Verified: | July 2018 |
Keywords provided by Gudrun Fleischhack, University Hospital, Essen:
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brain tumor relapse children |
etoposide intraventricular temozolomide |
Additional relevant MeSH terms:
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Brain Neoplasms Ependymoma Medulloblastoma Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site 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 Carboplatin Etoposide Etoposide phosphate Temozolomide Thiotepa Trofosfamide Cyclophosphamide Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors |