Chemotherapy and Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Neuroblastoma Study Phase II Study of Various Therapies in Patients With Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00017225
• Other study ID #: GPOH-GERMANY-NB97
• Secondary ID: CDR0000068664EU-
• Status: Completed
• Phase: Phase 2
• First received: June 6, 2001
• Last updated: August 1, 2013
• Start date: May 1997
• Est. completion date: February 2002

Study information

• Verified date: August 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: February 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed neuroblastoma

• Observation stratum:

• MYCN gene not amplified

• Infants with stage I-IVS disease OR

• Over 1 year of age and stage I or II resectable disease

• Standard-risk stratum:

• MYCN gene not amplified

• Infants with serious symptoms and stage II-IVS disease OR

• Over 1 year of age with stage II or III unresectable disease

• High-risk stratum:

• Stage IV disease OR

• Stage I-IVS MYCN gene-amplified disease

PATIENT CHARACTERISTICS:

Age:

• 20 and under

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• No kidney insufficiency

Cardiovascular:

• No cardiac insufficiency

Other:

• Not pregnant

• Fertile patients must use effective contraception

• No other serious illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy within 6 months after diagnosis

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Biological:
• filgrastim

Drug:
• carboplatin

• cisplatin

• cyclophosphamide

• dacarbazine

• doxorubicin hydrochloride

• etoposide

• ifosfamide

• melphalan

• tretinoin

• vincristine sulfate

• vindesine

Procedure:
• autologous bone marrow transplantation

• conventional surgery

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Germany	Urologische Klinik - Universitaetsklinikum Aachen	Aachen
Germany	Kinderkrankenhaus Josefinum	Augsburg
Germany	Zentralklinikum Augsburg	Augsburg
Germany	Caritaskrankenhaus	Bad Mergentheim
Germany	Klinikum Bayreuth	Bayreuth
Germany	Charite - Campus Virchow Klinikum	Berlin
Germany	Helios Klinikum Berlin	Berlin
Germany	Krankenanstalten Gilead	Biefeld
Germany	Kinderklinik der Universitaet-Bonn	Bonn
Germany	Stadt Klinikum - Howedestrase	Braunschweig
Germany	Zentralkrankenhaus	Bremen
Germany	Klinikum Chemnitz GMBH	Chemnitz
Germany	Klinikum Coburg	Coburg
Germany	Medizinische Universitaetsklinik I	Cologne
Germany	Carl - Thiem - Klinkum Cottbus	Cottbus
Germany	Vestische Kinderklinik	Datteln
Germany	Klinikum Lippe - Detmold	Detmold
Germany	Stadt. Kliniken	Dortmund
Germany	Stadt. KH Dresden - Neustadt	Dresden
Germany	Universitatsklinikum Carl Gustav Carl Carus	Dresden
Germany	Universitaetsklinik Duesseldorf	Duesseldorf
Germany	Helios Klinikum Erfurt GmbH	Erfurt
Germany	Universitaets - Kinderklinik	Erlangen
Germany	Universitaetsklinikum Essen	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Universitaetskinderklinik - Universitaetsklinikum Freiburg	Freiburg
Germany	Stadt. Kinderklinik	Gelsenkirchen
Germany	Kinderklinik	Giessen
Germany	Universitaetsklinikum Goettingen	Goettingen
Germany	Universitats - Kinderklinik	Greiswald
Germany	Kreiskrankenhaus Gummersbach GMBH	Gummersbach
Germany	Martin Luther Universitaet	Halle
Germany	St. Barbara Krankenhaus	Halle
Germany	Altonaer Kinderkrankenhaus	Hamburg
Germany	Universitaets-Krankenhaus Eppendorf	Hamburg
Germany	Evangelische Krankenhaus Hamm	Hamm
Germany	Kinderkrankenhaus auf der Bult	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaets-Kinderklinik Heidelberg	Heidelberg
Germany	Gemeinschaftskrankenhaus	Herdecke
Germany	Marien Hospital	Homburg
Germany	Universitatsklinik Homburg	Homburg
Germany	Praxis am Evangelischen Krankenhaus Bethanien	Iserlohn
Germany	Universitaets - Kinderklinik	Jena
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Stadt. Kinderklinik	Karlsruhe
Germany	Kinderkrankenhaus	Kassel
Germany	Klinikum Kassel	Kassel
Germany	Staedtische Krankenhaus Kiel	Kiel
Germany	University Hospital Schleswig-Holstein - Kiel Campus	Kiel
Germany	Stadt. Krankenhaus Kemperhof	Koblenz
Germany	Staedtisches Kinderkrankenhaus	Koln - Riehl
Germany	Klinik Konstanz	Konstanz
Germany	Klinikum Krefeld GmbH	Krefeld
Germany	Universitaets - Kinderklinik	Leipzig
Germany	Universitaets Klinik fuer Kinderchirurgie	Leipzig
Germany	Universitaets - Kinderklinik - Luebeck	Lubeck
Germany	St. Annastift Krankenhaus	Ludwigshafen
Germany	Universitatsklinikum der MA	Magdeburg
Germany	Johannes Gutenberg University	Mainz
Germany	Stadt. Klinik - Kinderklinik	Mannheim
Germany	Universitaets - Kinderklinik	Marburg
Germany	Klinikum Minden	Minden
Germany	Klinik und Poliklinik fuer Kinderheilkunde - Universitaetsklinikum Muenster	Muenster
Germany	Kinderklinik	Munich
Germany	Kinderklinik d. TU / Schwabing	Munich
Germany	Staedtisches Krankenhaus Muenchen - Harlaching	Munich
Germany	Universitaets - Kinderpoliklinik	Munich
Germany	Kinderklinik Kohlhof	Neunkirchen
Germany	Cnopfche Kinderklinik	Nuernberg
Germany	Klinikum Oldenburg	Oldenburg
Germany	Kindershospital	Osnabruck
Germany	Krankenhaus D Barmherzigen Brueder	Regensburg
Germany	Staedtische Klinikum-Kinderklinik	Rosenheim
Germany	Kinderklinik - Universitaetsklinikum Rostock	Rostock
Germany	Saarbrucker Winterbergkliniken	Saarbrucken
Germany	Diakone - Krankenhaus	Schwabisch Hall
Germany	Klinikum Schwerin	Schwerin
Germany	Leopoldina - Krankenhaus	Schwienfurt
Germany	Deutsches Rotes Kreuz	Siegen
Germany	Johanniter-Kinderklinik	St. Augustin
Germany	Olgahospital	Stuttgart
Germany	Mutterhaus der Borromaerinnen	Trier
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitaet Ulm	Ulm
Germany	St. Marien Hospital	Vechta
Germany	Reinhard - Nieter - Krankenhaus	Wilhelmshaven
Germany	Universitaets - Kinderklinik Wuerzburg	Wuerzburg
Germany	Helios Klinikum Wuppertal	Wuppertal
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Switzerland	University Children's Hospital	Basel
Switzerland	Ospedale "la Carita", Locarno	Locarno
Switzerland	Kinderspital Luzerne	Luzerne 16
Switzerland	University Children's Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Countries where clinical trial is conducted

Germany,  Netherlands,  Switzerland, 

References & Publications (12)

Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C. Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett. 2003 Jul 18;197(1-2):11-7. — View Citation

Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG, Schwabe D, Schilling FH, Benz-Bohm G, Berthold F. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol. 2008 Mar 20;26(9):1504-10. doi: 10.1200/JCO.2007.12.3349. — View Citation

Krams M, Hero B, Berthold F, Parwaresch R, Harms D, Rudolph P. Proliferation marker KI-S5 discriminates between favorable and adverse prognosis in advanced stages of neuroblastoma with and without MYCN amplification. Cancer. 2002 Feb 1;94(3):854-61. — View Citation

Kremens B, Hero B, Esser J, Weinel P, Filger-Brillinger J, Fleischhack G, Graf N, Grüttner HP, Niemeyer C, Schulz A, Wickmann L, Berthold F. Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14.18 for neuroblastoma. Cancer Immun — View Citation

Simon T, Hero B, Benz-Bohm G, von Schweinitz D, Berthold F. Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial. Pediatr Blood Cancer. 2008 May;50(5):965-9. — View Citation

Simon T, Hero B, Bongartz R, Schmidt M, Müller RP, Berthold F. Intensified external-beam radiation therapy improves the outcome of stage 4 neuroblastoma in children > 1 year with residual local disease. Strahlenther Onkol. 2006 Jul;182(7):389-94. — View Citation

Simon T, Hero B, Dupuis W, Selle B, Berthold F. The incidence of hearing impairment after successful treatment of neuroblastoma. Klin Padiatr. 2002 Jul-Aug;214(4):149-52. — View Citation

Spitz R, Hero B, Ernestus K, Berthold F. Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res. 2003 Jan;9(1):52-8. — View Citation

Spitz R, Hero B, Ernestus K, Berthold F. FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high-risk groups in neuroblastoma. Med Pediatr Oncol. 2003 Jul;41(1):30-5. — View Citation

Spitz R, Hero B, Ernestus K, Berthold F. Gain of distal chromosome arm 17q is not associated with poor prognosis in neuroblastoma. Clin Cancer Res. 2003 Oct 15;9(13):4835-40. — View Citation

Spitz R, Hero B, Westermann F, Ernestus K, Schwab M, Berthold F. Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations. Genes Chromosomes Cancer. 2002 Jul;34(3):299-305. — View Citation

von Schweinitz D, Hero B, Berthold F. The impact of surgical radicality on outcome in childhood neuroblastoma. Eur J Pediatr Surg. 2002 Dec;12(6):402-9. — View Citation

* Note: There are 12 references in all — Click here to view all references