Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children - Full Text View

Purpose

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	Intervention	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: trofosfamide/etoposide	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Childhood Brain Tumors

Drug Information available for: Thiotepa Etoposide Carboplatin Temozolomide Etoposide phosphate

U.S. FDA Resources

Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	160
Study Start Date:	February 2006
Estimated Study Completion Date:	January 2016
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1: P-HIT-REZ 2005 intravenous chemotherapy with carboplatin/etoposide	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: thiotepa, carboplatin, etoposide HD-chemotherapy prior to 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: 2: P-HIT-REZ 2005 oral chemotherapy with temozolomide	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: 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
Experimental: 3: E-HIT-REZ 2005 Phase II	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: 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: Intravent. Etoposide Phase II	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

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)

Eligibility

Ages Eligible for Study:	3 Months to 30 Years
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749723

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

More Information

Additional Information:

German Society of Pediatric Hematology and Oncology This link exits the ClinicalTrials.gov site

German Children's Cancer Foundation This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gudrun Fleischhack, MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen, University Hospital, Essen
ClinicalTrials.gov Identifier:	NCT00749723 History of Changes
Other Study ID Numbers:	EUDRACT 2005-002618-40, BfArM-4030755, EC-105/05, DKS 2006.01, DK 2008.17
Study First Received:	September 5, 2008
Last Updated:	April 25, 2013
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital, Bonn:

brain tumor
relapse
children

etoposide
intraventricular
temozolomide

Additional relevant MeSH terms:

Brain Neoplasms
Ependymoma
Medulloblastoma
Neuroectodermal Tumors, Primitive
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
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
Etoposide
Etoposide phosphate
Temozolomide
Trofosfamide
Thiotepa
Dacarbazine
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on May 16, 2013

Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children (HIT-REZ-2005)