Ependymomas, Medulloblastomas, Recurrent Brain Tumors, Supratentorial PNETs
Conditions
Keywords
brain tumor, relapse, children, etoposide, intraventricular, temozolomide
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)
Interventions
DRUGetoposide
100mg/m²/d continuously IV on day 1-4 of each 21-28 day cycle. Number of cycles: until disease progression, maximum 4 cycles
DRUGcarboplatin
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
DRUGtemozolomide
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
DRUGthiotepa, carboplatin, etoposide
high dose chemotherapy followed by to autologous stem cell transplantation
DRUGtemozolomide, thiotepa
high dose chemotherapy followed by autologous stem cell transplantation
PROCEDUREautologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy
DRUGintraventricular 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
DRUGtrofosfamide, 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
Sponsors
University Hospital, Bonn
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course | 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 | 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 | 6 weeks for each patient (8 years for the whole study population) | disease stabilization rate (CR+PR+SD/all patients) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC) | 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: PFS and OS from start of therapy | 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) | 8 years | rate of adverse events of CTC°1-4 according to CTCAE v3.0 |
| P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms | 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 | 10 years | progression free and overall survival from start of therapy until PD, last follow up or death, respectively |
Countries
Germany
Outcome results
None listed