Overview

This trial is active, not recruiting.

Conditions recurrent brain tumors, supratentorial pnets, medulloblastomas, ependymomas
Treatments carboplatin, etoposide, temozolomide, thiotepa, carboplatin, etoposide, temozolomide, thiotepa, autologous stem cell transplantation, trofosfamide/etoposide
Phase phase 2/phase 3
Sponsor University Hospital, Bonn
Start date February 2006
End date January 2013
Trial size 160 participants
Trial identifier NCT00749723, BfArM-4030755, DKS 2006.01, DK 2008.17, EC-105/05, EUDRACT 2005-002618-40

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
intravenous chemotherapy with carboplatin/etoposide
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
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
thiotepa, carboplatin, etoposide
HD-chemotherapy prior to stem cell transplantation
autologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy
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
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)
oral chemotherapy with temozolomide
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
temozolomide, thiotepa
HD-chemotherapy prior to autologous stem cell transplantation
autologous stem cell transplantation
autologous stem cell transplantation following HD-chemotherapy
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)
Phase II
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
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
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)
Phase II
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

Primary Outcomes

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
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

Secondary Outcomes

Measure
P-HIT-REZ 2005 study: two Chemotherapy-arms: overall survival from start of therapy
time frame: 10 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: 8 years
P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms
time frame: 8 years

Eligibility Criteria

Male or female participants from 3 months up to 30 years old.

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

Additional Information

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
Principal investigator Gudrun Fleischhack, MD
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)
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by University Hospital, Bonn.