Chemotherapy and Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma
- Conditions
- Neuroblastoma
- Registration Number
- NCT00017225
- Lead Sponsor
- German Society for Pediatric Oncology and Hematology GPOH gGmbH
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Combining these therapies may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and radiation therapy with or without peripheral stem cell transplantation in treating patients who have neuroblastoma.
- Detailed Description
OBJECTIVES:
* Determine the frequency of spontaneous remission in pediatric patients with localized neuroblastoma.
* Determine the course of regression in patients with spontaneous remission.
* Determine the event-free survival rate of patients with high-risk neuroblastoma treated with maintenance chemotherapy OR consolidation chemotherapy followed by autologous stem cell rescue.
* Determine if a correlation exists between long-term overall survival and catecholamine response in these high-risk patients.
* Determine if a correlation exists between cytotoxic and conditioning chemotherapies, in terms of bone marrow toxicity, in these high-risk patients.
OUTLINE: This is a multicenter study. Patients are stratified according to risk (low vs standard vs high).
* Observation stratum (low risk): Patients undergo surgical biopsy followed by observation for 6-12 months. Patients may also undergo second-look surgery. Patients with tumor regression receive no further therapy. Patients with disease progression or no tumor regression receive standard-risk chemotherapy as in the standard-risk stratum.
* Standard-risk stratum: Patients undergo surgical biopsy. Patients at least 6 months of age receive 1 course of chemotherapy comprising cisplatin IV and etoposide IV continuously on days 1-4 and vindesine IV over 1 hour on day 1. Patients then receive 1 course of chemotherapy comprising vincristine IV over 1 hour on days 1 and 8, dacarbazine IV over 1 hour on days 1-5, ifosfamide IV continuously on days 1-5, and doxorubicin IV over 4 hours on days 6 and 7.
Patients under 6 months of age receive doxorubicin IV over 30 minutes and vincristine IV on days 1, 3, and 5 and cyclophosphamide IV over 5 minutes on days 1-7. Treatment repeats every 3 weeks for 2 courses in the absence of unacceptable toxicity.
After chemotherapy, patients may undergo second-look surgery followed by 2 additional courses of chemotherapy as above. Patients with complete response or very good partial response receive no further therapy. Patients with partial response, minimal response, no response, or progressive disease undergo local radiotherapy daily 5 days a week for approximately 6 weeks. Patients with no response after radiotherapy may then receive therapy as in the high-risk stratum.
* High-risk stratum: Patients undergo surgical biopsy. Patients at least 6 months of age receive induction chemotherapy comprising cisplatin, etoposide, and vindesine as in the standard-risk stratum combined with filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 8 and continuing until blood counts recover. Patients also receive alternating courses of vincristine, dacarbazine, ifosfamide, and doxorubicin as in the standard-risk stratum combined with G-CSF SC daily beginning on day 9 and continuing until blood counts recover. Treatment repeats every 3 weeks for up to 6 courses in the absence of unacceptable toxicity.
Patients under 6 months of age receive 2 courses of induction chemotherapy as in the standard-risk stratum followed by 4 courses of alternating chemotherapy as above.
Patients may also undergo second-look surgery.
Patients then receive consolidation chemotherapy comprising melphalan IV over 30 minutes on days -8 to -5, etoposide IV over 4 hours on day -4, and carboplatin IV over 1 hour on days -4 to -2. Patients undergo autologous stem cell transplantation (ASCT) on day 0. Patients also receive G-CSF SC or IV over 2 hours daily beginning on day 0. Patients may then undergo radiotherapy daily 5 days a week for 6 weeks.
Patients who were diagnosed less than 1 year ago and who do not demonstrate MYCN amplication receive maintenance chemotherapy comprising oral cyclophosphamide on days 1-8 (instead of consolidation chemotherapy and ASCT as above). Treatment repeats every 3 weeks for 4 courses.
Beginning 4-6 weeks after transplantation or 4 weeks after initiation of the last course of maintenance chemotherapy, all patients receive consolidation therapy with oral tretinoin 3 times daily on days 1-14. Treatment repeats every 28 days for 6 courses followed by a 3-month rest. Patients then receive 3 additional courses.
Patients are followed at 6 weeks, every 3 months for 5 years, and then every 6 months thereafter.
PROJECTED ACCRUAL: Approximately 130 patients (50 in high-risk stratum, 15 in standard-risk stratum, and 65 in observation stratum) will be accrued for this study within 1 year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (88)
Carl - Thiem - Klinkum Cottbus
🇩🇪Cottbus, Germany
Klinikum Lippe - Detmold
🇩🇪Detmold, Germany
Praxis am Evangelischen Krankenhaus Bethanien
🇩🇪Iserlohn, Germany
University Hospital Schleswig-Holstein - Kiel Campus
🇩🇪Kiel, Germany
Westpfalz-Klinikum GmbH
🇩🇪Kaiserslautern, Germany
Klinikum Kassel
🇩🇪Kassel, Germany
Stadt. Krankenhaus Kemperhof
🇩🇪Koblenz, Germany
Klinikum Minden
🇩🇪Minden, Germany
Universitaets - Kinderklinik - Luebeck
🇩🇪Lubeck, Germany
St. Annastift Krankenhaus
🇩🇪Ludwigshafen, Germany
Klinik und Poliklinik fuer Kinderheilkunde - Universitaetsklinikum Muenster
🇩🇪Muenster, Germany
Universitaets - Kinderpoliklinik
🇩🇪Munich, Germany
Stadt. Klinik - Kinderklinik
🇩🇪Mannheim, Germany
Staedtisches Krankenhaus Muenchen - Harlaching
🇩🇪Munich, Germany
Cnopfche Kinderklinik
🇩🇪Nuernberg, Germany
Kindershospital
🇩🇪Osnabruck, Germany
Kinderklinik Kohlhof
🇩🇪Neunkirchen, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Krankenhaus D Barmherzigen Brueder
🇩🇪Regensburg, Germany
Kinderklinik - Universitaetsklinikum Rostock
🇩🇪Rostock, Germany
Diakone - Krankenhaus
🇩🇪Schwabisch Hall, Germany
Universitaet Ulm
🇩🇪Ulm, Germany
Reinhard - Nieter - Krankenhaus
🇩🇪Wilhelmshaven, Germany
Medizinische Universitaetsklinik I
🇩🇪Cologne, Germany
Urologische Klinik - Universitaetsklinikum Aachen
🇩🇪Aachen, Germany
Klinikum Bayreuth
🇩🇪Bayreuth, Germany
Stadt Klinikum - Howedestrase
🇩🇪Braunschweig, Germany
Kinderkrankenhaus Josefinum
🇩🇪Augsburg, Germany
Helios Klinikum Berlin
🇩🇪Berlin, Germany
Zentralklinikum Augsburg
🇩🇪Augsburg, Germany
Caritaskrankenhaus
🇩🇪Bad Mergentheim, Germany
Universitaets Klinik fuer Kinderchirurgie
🇩🇪Leipzig, Germany
Vestische Kinderklinik
🇩🇪Datteln, Germany
Kinderklinik d. TU / Schwabing
🇩🇪Munich, Germany
Klinikum Coburg
🇩🇪Coburg, Germany
Zentralkrankenhaus
🇩🇪Bremen, Germany
Staedtische Krankenhaus Kiel
🇩🇪Kiel, Germany
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
Klinikum Chemnitz GMBH
🇩🇪Chemnitz, Germany
Universitatsklinikum Carl Gustav Carl Carus
🇩🇪Dresden, Germany
University Children's Hospital
🇨ðŸ‡Zurich, Switzerland
Kinderspital Luzerne
🇨ðŸ‡Luzerne 16, Switzerland
Johanniter-Kinderklinik
🇩🇪St. Augustin, Germany
Universitaets - Kinderklinik Wuerzburg
🇩🇪Wuerzburg, Germany
St. Marien Hospital
🇩🇪Vechta, Germany
Helios Klinikum Wuppertal
🇩🇪Wuppertal, Germany
Altonaer Kinderkrankenhaus
🇩🇪Hamburg, Germany
Klinikum Krefeld GmbH
🇩🇪Krefeld, Germany
Universitatsklinikum der MA
🇩🇪Magdeburg, Germany
Johannes Gutenberg University
🇩🇪Mainz, Germany
Staedtisches Kinderkrankenhaus
🇩🇪Koln - Riehl, Germany
Kinderklinik
🇩🇪Munich, Germany
Universitatsklinik Homburg
🇩🇪Homburg, Germany
Universitats - Kinderklinik
🇩🇪Greiswald, Germany
Ospedale "la Carita", Locarno
🇨ðŸ‡Locarno, Switzerland
Leopoldina - Krankenhaus
🇩🇪Schwienfurt, Germany
Saarbrucker Winterbergkliniken
🇩🇪Saarbrucken, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Staedtische Klinikum-Kinderklinik
🇩🇪Rosenheim, Germany
Marien Hospital
🇩🇪Homburg, Germany
Kinderkrankenhaus
🇩🇪Kassel, Germany
Gemeinschaftskrankenhaus
🇩🇪Herdecke, Germany
Mutterhaus der Borromaerinnen
🇩🇪Trier, Germany
Klinikum Schwerin
🇩🇪Schwerin, Germany
Olgahospital
🇩🇪Stuttgart, Germany
Deutsches Rotes Kreuz
🇩🇪Siegen, Germany
Kinderklinik der Universitaet-Bonn
🇩🇪Bonn, Germany
Charite - Campus Virchow Klinikum
🇩🇪Berlin, Germany
Krankenanstalten Gilead
🇩🇪Biefeld, Germany
Universitaetsklinik Duesseldorf
🇩🇪Duesseldorf, Germany
Stadt. Kliniken
🇩🇪Dortmund, Germany
Stadt. KH Dresden - Neustadt
🇩🇪Dresden, Germany
Helios Klinikum Erfurt GmbH
🇩🇪Erfurt, Germany
Universitaets - Kinderklinik
🇩🇪Marburg, Germany
Stadt. Kinderklinik
🇩🇪Karlsruhe, Germany
Universitaetsklinikum Goettingen
🇩🇪Goettingen, Germany
Universitaetskinderklinik - Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Kreiskrankenhaus Gummersbach GMBH
🇩🇪Gummersbach, Germany
Universitaets-Krankenhaus Eppendorf
🇩🇪Hamburg, Germany
Martin Luther Universitaet
🇩🇪Halle, Germany
Evangelische Krankenhaus Hamm
🇩🇪Hamm, Germany
Universitaets-Kinderklinik Heidelberg
🇩🇪Heidelberg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Kinderkrankenhaus auf der Bult
🇩🇪Hannover, Germany
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Universitaetsklinikum Essen
🇩🇪Essen, Germany
St. Barbara Krankenhaus
🇩🇪Halle, Germany
Klinik Konstanz
🇩🇪Konstanz, Germany