Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children

NCT00749723 | Completed Phase 2 DMC

• 4 other identifiers: EUDRACT 2005-002618-40BfArM-4030755EC-105/05DKS 2006.01, 2008.17, 2012.03
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 54

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.

Conditions

Recurrent Brain Tumors; Supratentorial PNETs; Medulloblastomas; Ependymomas

Keywords

brain tumor; relapse; children; etoposide; intraventricular; temozolomide

Outcome Measures

Primary Outcomes (3)

• P-HIT-REZ 2005 study: two Chemotherapy-arms: response evaluation after the fourth therapy course

  determination of objective repsonse rate (CR+PR)

  4 months for each patient (8 years for the whole study population)

• E-HIT-REZ 2005 study (Phase II Study "Oral chemotherapy with temozolomide"): Evaluation of response rate to the 60-days oral chemotherapy with temozolomide

  determination of objective repsonse rate (CR+PR/all patients)

  2 months for each patient (8 years for the whole study population)

• Phase II study "Intraventricular therapy with etoposide": Evaluation of response rate to the 5-week intraventricular therapy with etoposide

  disease stabilization rate (CR+PR+SD/all patients)

  6 weeks for each patient (8 years for the whole study population)

Secondary Outcomes (5)

• P-HIT-REZ 2005 study: two Chemotherapy-arms: PFS and OS from start of therapy

  10 years

• P-HIT-REZ 2005 study: two Chemotherapy-arms: toxicity rate (CTC) in both arms

  8 years

• E-HIT-REZ 2005 study: Chemotherapy-arm: PFS and OS from start of therapy

  10 years

• E-HIT-REZ 2005 study: Chemotherapy-arm: toxicity rate (CTC)

  10 years

• Phase II study "Intraventricular therapy with etoposide": toxicity rate (CTC)

  8 years

Study Arms (4)

1: P-HIT-REZ 2005

EXPERIMENTAL

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

Drug: carboplatin; Drug: etoposide; Drug: thiotepa, carboplatin, etoposide; Procedure: autologous stem cell transplantation; Drug: intraventricular etoposide; Drug: trofosfamide, etoposide

2: P-HIT-REZ 2005

EXPERIMENTAL

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

Drug: temozolomide; Drug: temozolomide, thiotepa; Procedure: autologous stem cell transplantation; Drug: intraventricular etoposide

3: E-HIT-REZ 2005

EXPERIMENTAL

Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide

Drug: temozolomide; Drug: intraventricular etoposide; Drug: trofosfamide, etoposide

Intraventricular Etoposide

EXPERIMENTAL

Phase II, intraventricular chemotherapy with etoposide

Drug: intraventricular etoposide

Interventions

carboplatin DRUG

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

Also known as: Carboplatin IV

1: P-HIT-REZ 2005

etoposide DRUG

100mg/m²/d continuously IV on day 1-4 of each 21-28 day cycle. Number of cycles: until disease progression, maximum 4 cycles

Also known as: etoposide IV

1: P-HIT-REZ 2005

temozolomide DRUG

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

Also known as: temozolomide orally

2: P-HIT-REZ 2005; 3: E-HIT-REZ 2005

thiotepa, carboplatin, etoposide DRUG

high dose chemotherapy followed by to autologous stem cell transplantation

Also known as: thiotepa, carboplatin, etoposide IV, high dose

1: P-HIT-REZ 2005

temozolomide, thiotepa DRUG

high dose chemotherapy followed by autologous stem cell transplantation

Also known as: temozolomide, thiotepa IV

2: P-HIT-REZ 2005

autologous stem cell transplantation PROCEDURE

autologous stem cell transplantation following HD-chemotherapy

Also known as: ASCT

1: P-HIT-REZ 2005; 2: P-HIT-REZ 2005

intraventricular etoposide DRUG

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

Also known as: etoposide intra-CSF

1: P-HIT-REZ 2005; 2: P-HIT-REZ 2005; 3: E-HIT-REZ 2005; Intraventricular Etoposide

trofosfamide, etoposide DRUG

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

Also known as: trofosfamide, etoposide orally

1: P-HIT-REZ 2005; 3: E-HIT-REZ 2005

Eligibility Criteria

• Age: 3 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (54)

Universitätskinderklinik Aachen

Aachen, 52074, Germany

Location

Klinikum Augsburg, Klinik für Kinder- und Jugendmedizin

Augsburg, 86156, Germany

Location

Helios Klinikum Berlin-Buch, Klinik für Kinderheilkunde und Jugendmedizin

Berlin, 13125, Germany

Location

Charité Klinikum Campus Virchow, Kinderklinik

Berlin, 13353, Germany

Location

Klinik ür Kinder- und Jugendmedizin in Bethel

Bielefeld, 33617, Germany

Location

Universitätskinderklinik Bonn

Bonn, 53113, Germany

Location

Städtisches Klinikum Braunschweig, Kinderklinik

Braunschweig, 38118, Germany

Location

Klinikum Bremen-Mitte

Bremen, 28177, Germany

Location

Universitätskinderklinik Köln

Cologne, 50924, Germany

Location

Carl-Thiele-Klinikum Cottbus, Zentrum für Kinderheilkunde

Cottbus, 03048, Germany

Location

Vestische Kinder- und Jugendklinik Datteln

Datteln, 45711, Germany

Location

Klinikum Dortmund, Klinik für Kinder- und Jugendmedizin

Dortmund, 44137, Germany

Location

Universitätsklinikum Dresden, Kinderklinik

Dresden, 01307, Germany

Location

Klinikum Duisburg, Klinik für Kinder-und Jugendmedizin

Duisburg, 47055, Germany

Location

Universitätskinderklinik Düsseldorf

Düsseldorf, 40225, Germany

Location

Helios Klinikum Erfurt, Zentrum für Kinderheilkunde

Erfurt, 99089, Germany

Location

Universitätskinderklinik Erlangen

Erlangen, 91054, Germany

Location

Universitätskinderklinik Essen

Essen, 45122, Germany

Location

Klinikum der Wolfgang Goethe Universität, Klinik für Kinderheilkunde

Frankfurt am Main, 60590, Germany

Location

Universitätskinderklinik Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Gießen und Marburg, Zentrum für Kinderheilkunde

Giessen, 35385, Germany

Location

Universitätskinderklinik Göttingen

Göttingen, 37075, Germany

Location

Universitätskinderklinik Greifswald

Greifswald, 17475, Germany

Location

Martin-Luther-Universität Halle Wittenberg

Halle, 06120, Germany

Location

Universitätskinderklinik Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule, Zentrum für Kinderheilkunde

Hanover, 30625, Germany

Location

Universitätskinderklinik Heidelberg

Heidelberg, 69120, Germany

Location

SLK Kinderklinik Heilbronn

Heilbronn, 74078, Germany

Location

Gemeinschaftskrankenhaus Herdecke, Kinderklinik

Herdecke, 58313, Germany

Location

Universitätskinderklinik

Homburg/Saar, 66421, Germany

Location

Friedrich Schiller Universität, Klinik für Kinder-und Jugendmedizin

Jena, 07745, Germany

Location

Städtisches Krankenhaus, Klinik für Kinder- und Jugendmedizin

Karlsruhe, 76133, Germany

Location

Klinikum Kassel, Kinderklinik

Kassel, 34125, Germany

Location

UKSH, Campus Kiel, Klinik für Allg. Pädiatrie

Kiel, 24105, Germany

Location

Städtisches Klinikum Kemperhof, Klinik für Kinder- und Jugendmedizin

Koblenz, 56073, Germany

Location

Universitätskinderklinik Leipzig

Leipzig, 04317, Germany

Location

Universitätskinderklinik Lübeck

Lübeck, 23538, Germany

Location

Otto-von-Guericke-Universität, Zentrum für Kinderheilkunde

Magdeburg, 39120, Germany

Location

Universitätskinderklinik Mainz

Mainz, 55131, Germany

Location

Universitätskinderklinik Mannheim

Mannheim, 68167, Germany

Location

Universitätskinderklinik Marburg

Marburg, 35043, Germany

Location

Klinikum Minden III, Klinik für Kinder-und Jugendheilkunde

Minden, 32432, Germany

Location

Dr. von Haunersches Kinderspital

München, 80337, Germany

Location

Städtisches Krankenhaus München-Schwabing, Kinderklinik der TU München

München, 80804, Germany

Location

Universitätskinderklinik Münster

Münster, 48129, Germany

Location

Cnopf'sche Kinderklinik

Nuremberg, 90419, Germany

Location

Klinikum Oldenburg, Zentrum für Kinder-und Jugendmedizin

Oldenburg, 26131, Germany

Location

Universitäts-Kinderklinik

Regensburg, 93042, Germany

Location

Universitätskinderklinik Rostock

Rostock, 18057, Germany

Location

Asklepios Klinik Sankt Augustin GmbH

Sankt Augustin, 53757, Germany

Location

Olgahospital-Pädiatrisches Zentrum

Stuttgart, 70176, Germany

Location

Universitätskinderklinik Tübingen

Tübingen, 72076, Germany

Location

Univeritätsklinikum Ulm, Abteilung Kinder-und Jugendmedizin

Ulm, 89075, Germany

Location

Universitätskinderklinik Würzburg

Würzburg, 97080, Germany

Location

Related Links

• German Society of Pediatric Hematology and Oncology
• German Children's Cancer Foundation

MeSH Terms

Conditions

Brain Neoplasms; Medulloblastoma; Ependymoma; Recurrence

Interventions

Carboplatin; Etoposide; Temozolomide; Thiotepa; trofosfamide

Condition Hierarchy (Ancestors)

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; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines

Study Officials

• Gudrun Fleischhack, MD

  Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Department of Pediatric Hematology & Oncology, Pediatrics III, University Children's Hospital Essen

Study Record Dates

• First Submitted: September 5, 2008
• First Posted: September 9, 2008
• Study Start: February 1, 2006
• Primary Completion: January 31, 2015
• Study Completion: January 31, 2016
• Last Updated: July 20, 2018

Record last verified: 2018-07

Locations

DE (54)