Observation, Combination Chemotherapy, Radiation Therapy, and/or Autologous Stem Cell Transplant in Treating Young Patients With Neuroblastoma - Full Text View

Sponsored by:	Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00410631

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. This may allow more chemotherapy to be given so that more tumor cells are killed. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether observation is more effective than combination chemotherapy, radiation therapy, and/or autologous stem cell transplant in treating neuroblastoma.

PURPOSE: This randomized phase III and phase IV trial is studying observation, combination chemotherapy, radiation therapy, and/or autologous stem cell transplant to compare how well they work in treating young patients with neuroblastoma.

Condition	Intervention	Phase
Neuroblastoma	Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide phosphate Drug: ifosfamide Drug: isotretinoin Drug: melphalan Drug: topotecan hydrochloride Drug: vincristine sulfate Drug: vindesine Procedure: autologous hematopoietic stem cell transplantation Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: iobenguane I 131 Radiation: radiation therapy	Phase III

MedlinePlus related topics: Cancer Neuroblastoma Radiation Therapy Surgery

Drug Information available for: Cyclophosphamide Vincristine Cisplatin Doxorubicin Doxorubicin hydrochloride Etoposide Carboplatin Vindesine 3-Iodobenzylguanidine Iobenguane Myocet Etoposide phosphate Topotecan hydrochloride Filgrastim Topotecan Melphalan Vincristine sulfate Ifosfamide Dacarbazine Isotretinoin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	NB2004 Trial Protocol for Risk Adapted Treatment of Children With Neuroblastoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival (EFS) [ Designated as safety issue: No ]
Locoregional EFS [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time from diagnosis to transition to stage 4 disease, to death from disease, or to the last follow-up (if no transition to stage 4 disease is observed) [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to the beginning of primary tumor regression (in patients in the low-risk group [LRG]) [ Designated as safety issue: No ]
Time to the normalization of tumor markers HVA and VMA in urine [ Designated as safety issue: No ]
Time to no evidence of disease (in patients in the LRG with stage 4S disease) [ Designated as safety issue: No ]
Status of the primary tumor 12 months after diagnosis (LRG) [ Designated as safety issue: No ]
Best status of the primary tumor within the first 12 months (LRG) [ Designated as safety issue: No ]
Status of chromosome 1p (unblinded) and status of chromosome 11q (blinded) [ Designated as safety issue: No ]
Comparison of the extent of initial surgery (incomplete resection vs macroscopic complete resection) (LRG) [ Designated as safety issue: No ]
Comparison of the extent of best surgery during protocol treatment (incomplete resection vs macroscopic complete resection) [ Designated as safety issue: No ]
Surgery-related complications (i.e., bleeding, infection, intestinal obstruction, or other) [ Designated as safety issue: No ]
Disease progression and symptoms controlled after the first, second, third, and fourth N4 course (LRG) [ Designated as safety issue: No ]
Disease progression and symptoms not controlled after four N4 courses (LRG) [ Designated as safety issue: No ]
Transition to stage 4 disease at any time (LRG) [ Designated as safety issue: No ]
Acute and late side effects of external-beam radiotherapy (medium-risk group [MRG] and high-risk group [HRG]) [ Designated as safety issue: Yes ]
Early response after 2 courses of induction therapy (N5 and N6 or two courses of N8) (HRG) [ Designated as safety issue: No ]
Response to induction therapy prior to conditioning therapy or after 280 days (HRG) [ Designated as safety issue: No ]
Grade of toxicity observed during induction therapy course 1 (N5 or N8) (HRG) [ Designated as safety issue: Yes ]
Grade of toxicity observed during induction therapy course 2 (N6 or N8) (HRG) [ Designated as safety issue: Yes ]
Frequency of grade 3 or 4 toxicity observed during the last 6 courses of induction therapy (3 courses of N5 and N6) (HRG) [ Designated as safety issue: Yes ]
Activity and whole body dose of radiotherapy [ Designated as safety issue: No ]

Estimated Enrollment:	642
Study Start Date:	October 2004
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of neuroblastoma by histology using tumor tissue or as evidenced by the presence of distinct neuroblastoma cells in the bone marrow AND elevated catecholamine metabolites (i.e., homovanillic acid [HVA] and vanillylmandelic acid [VMA]) in blood or urine
- Newly diagnosed disease (for patients in the low-risk group)
- Diagnosis from tumor tissue (for patients in the medium-risk group)
Meets criteria for 1 of the following risk groups:
- Low-risk group
  - No MYCN amplification AND meets 1 of the following criteria:
    - Stage 1 disease
    - Stage 2 disease with no chromosome 1p deletion or imbalance
    - Stage 3 disease with no chromosome 1p deletion or imbalance (for patients < 2 years of age)
    - Stage 4S disease (for patients < 1 year of age)
- Medium-risk group
  - No MYCN amplification AND meets 1 of the following criteria:
    - Stage 2 disease with chromosome 1p deletion or imbalance
    - Stage 3 disease with chromosome 1p deletion or imbalance
      - Any chromosome 1p status (for patients ≥ 2 years of age)
    - Stage 4 disease (for patients < 1 year of age)
- High-risk group, meeting 1 of the following criteria:
  - Any stage disease with MYCN amplification
    - Any MYCN status (for patients ≥ 1 year of age)

PATIENT CHARACTERISTICS:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior nephrectomy or other mutilating surgery as initial surgery (for patients in the low-risk group)
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410631

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Locations

Germany
Allgemeinen Krankenhaus Celle Kinderklinik	Recruiting
Celle, Germany, 29223
Contact: Martin Kirschstein, MD 49-241-809-222 martin.kirschstein@akh-celle.de
Carl - Thiem - Klinkum Cottbus	Recruiting
Cottbus, Germany, D-03048
Contact: D Mobius, MD 49-355-462-336
Charite University Hospital - Campus Virchow Klinikum	Recruiting
Berlin, Germany, D-13353
Contact: Gunter Henze 49-30-450-566-004
Children's Hospital	Recruiting
Cologne, Germany, D-50924
Contact: Frank Berthold, MD 49-221-478-4380 frank.berthold@uk-koeln.de
Cnopf'sche Kinderklinik	Recruiting
Nuremberg, Germany, 90419
Contact: W. Scheurlen 49-911-334-002
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm	Recruiting
Ulm, Germany, D-89075
Contact: Klaus M. Debatin, MD 49-731-5002-7790 klaus-michael.debatin@medizin.uni-ulm.de
Dr. von Haunersches Kinderspital der Universitaet Muenchen	Recruiting
Munich, Germany, D-80337
Contact: Arndt Borkhardt 49-89-5160-2842
Evangelisches Krankenhauus Bielfeld	Recruiting
Biefeld, Germany, 33617
Contact: N. Jorch, MD 49-521-7727-8050
Gemeinschaftskrankenhaus	Recruiting
Herdecke, Germany, 58313
Contact: Christoph Tautz, MD 49-233-0620 ctautz@yahoo.de
Helios Kliniken Wuppertal University Hospital	Recruiting
Wuppertal, Germany, D-42283
Contact: K. Sinha, MD 49-202-896-2441
Helios Klinikum Berlin	Recruiting
Berlin, Germany, D-13125
Contact: L. Wickmann, MD 49-30-9401-2353 lwickmann@berlin.helios-kliniken.de
Helios Klinikum Erfurt	Recruiting
Erfurt, Germany, 99089
Contact: Axel Sauerbrey, MD 49-361-781-3702 asauerbrey@erfurt.helios-kliniken.de
Johannes Gutenberg University	Recruiting
Mainz, Germany, D-55101
Contact: P. Gutjahr, MD 49-6131-172-112
Johanniter-Kinderklinik	Recruiting
St. Augustin, Germany, 53757
Contact: Roswitha Dickerhoff, MD 49-2241-2490 roswitha.dickerhoft@uni-bonn.de
Kinderklinik - Universitaetsklinikum Aachen	Recruiting
Aachen, Germany, D-52074
Contact: R. Mertens, MD, PhD 49-241-809-222 rmertens@ukaachen.de
Kinderklinik - Universitaetsklinikum Rostock	Recruiting
Rostock, Germany, D-18057
Contact: Carl Friedrich Classen, MD, PD 49-381-4940 carl-friedrich.classen@med.uni-rostock.de
Kinderklinik der Universitaet Bonn	Recruiting
Bonn, Germany, D-53113
Contact: Udo Bode, MD 49-228-2873-3215 udo.bode@ukb.uni-bonn.de
Kinderklinik Kohlhof	Recruiting
Neunkirchen, Germany, D-66539
Contact: Contact Person 49-681-3630
Kinderklinik	Recruiting
Giessen, Germany, D-35385
Contact: Alfred Reiter, MD 49-641-994-3400
Kinderklink Siegen Deutsches Rotes Kreuz	Recruiting
Siegen, Germany, D-57072
Contact: Rainer Burghard, MD 49-271-23450 rainer.burghard@drk-kinderklinik.de
Klinikum Neubrandenburg	Recruiting
Neubrandenburg, Germany, 17036
Contact: H. J. Feickert, MD, PhD 49-395-775-2901 feickerthj@dbk-nb.de
Kinderkrankenhaus Park Schoenfeld	Recruiting
Kassel, Germany, D-34121
Contact: M. L. Wright, MD 49-561-928-5108
Klinik St. Hedwig-Kinderklinik	Recruiting
Regensburg, Germany, 93049
Contact: Ove Peters 49-941-3690
Kliniken der Stadt Koeln gGmbH - Kinderkrankenhaus Riehl	Recruiting
Cologne, Germany, D-50735
Contact: Contact Person 49-221-8907-5243
Klinikum am Bamberg	Recruiting
Bamberg, Germany, 96049
Contact: Gloeckel, MD 49-951-506-0
Klinikum Augsburg	Recruiting
Augsburg, Germany, DOH-86156
Contact: Astrid Gnekow 49-821-400-3603
Klinikum Bayreuth	Recruiting
Bayreuth, Germany, D-95445
Contact: T. Rupprecht 49-921-400-6202
Klinikum Bremen-Mitte	Recruiting
Bremen, Germany, D-28205
Contact: Arnulf Pekrun, MD, PhD 49-421-497-3656 arnulf.pekrun@klinikum-bremen-mitte.de
Klinikum Chemnitz gGmbH	Recruiting
Chemnitz, Germany, D-09116
Contact: Krause, MD 49-371-3332-4124
Klinikum Coburg	Recruiting
Coburg, Germany, 96450
Contact: Roland Frank, MD 49-8561-225-547
Klinikum der J.W. Goethe Universitaet	Recruiting
Frankfurt, Germany, D-60590
Contact: Thomas Klingebiel, MD 49-69-6301-5243 thomas.klingebiel@kgu.de
Klinikum der Universitaet Muenchen - Grosshadern Campus	Recruiting
Munich, Germany, D-81377
Contact: Schulz, MD 49-89-7095-2404
Klinikum Dortmund	Recruiting
Dortmund, Germany, D-44137
Contact: Heidi Olscheswski, MD 49-231-9532-1721
Klinikum Duisburg	Recruiting
Duisburg, Germany, D-47055
Contact: Ruef, MD 49-203-733-2421
Klinikum Kassel	Recruiting
Kassel, Germany, D-34125
Contact: Martina Rodehueser, MD 49-561-9800
Klinikum Kemperhof Koblenz	Recruiting
Koblenz, Germany, D-56065
Contact: M. Rister, MD 49-261-499-2602
Klinikum Krefeld GmbH	Recruiting
Krefeld, Germany, D-47805
Contact: S. Volpel, MD 49-2151-322-375
Klinikum Lippe - Detmold	Recruiting
Detmold, Germany, D-32756
Contact: Klaus Wesseler, MD 49-5231-724-510
Klinikum Minden	Recruiting
Minden, Germany, D-32423
Contact: W Tilmann, MD 49-571-801-4601
Kinderkrankenhaus auf der Bult	Recruiting
Hannover, Germany, 30173
Contact: U. Hofmann, MD 49-511-811-5424
Klinikum Oldenburg	Recruiting
Oldenburg, Germany, 26133
Contact: Hermann Mueller, MD 49-441-403-2013 mueller.hermann@klinikum-oldenburg.de
Krankenanstalt Mutterhaus der Borromaerinnen	Recruiting
Trier, Germany, D-54290
Contact: Wolfgang Rauh, MD 49-651-947-2620
Krankenhaus Muenchen Schwabing	Recruiting
Munich, Germany, 80804
Contact: Stefan Burdach, MD, PhD 49-89-3068-2276
Krankenhaus St. Elisabeth und St. Barbara	Recruiting
Halle, Germany, D-06110
Contact: G. Guenther, MD 49-345-213-4514
Medizinische Hochschule Hannover	Recruiting
Hannover, Germany, D-30625
Contact: Karl Welte, MD 49-511-532-9123 welte.karl.h@mh-hannover.de
Olgahospital	Recruiting
Stuttgart, Germany, D-70176
Contact: Stefan Bielack, MD 49-711-992-460 st.bielack@olgahospital.de
Reinhard-Nieter-Krankenhaus	Recruiting
Wilhelmshaven, Germany, D-26389
Contact: Liebner, MD 49-4421-891-840
SLK - Kliniken Heilbronn GmbH - Klinikum am Gesundbrunnen	Recruiting
Heilbronn, Germany, D-74064
Contact: Full, MD 49-7131-493-702
St. Annastift Krankenhaus	Recruiting
Ludwigshafen, Germany, 67065
Contact: Barbara Selle, MD 49-621-57021
Staedtisches Klinik - Kinderklinik	Recruiting
Mannheim, Germany, D-68167
Contact: M. Duerken 49-621-383-2244
Universitaets - Kinderklinik	Recruiting
Marburg, Germany, 35033
Contact: H. Christiansen, MD 49-6421-286-2650
Staedtisches Klinikum Karlsruhe gGmbH	Recruiting
Karlsruhe, Germany, 76133
Contact: A. Leipold 49-721-974-3230
Staedtisches Krankenhaus Muenchen - Harlaching	Recruiting
Munich, Germany, D-81545
Contact: Contact Person 49-89-6210-2443
Universitaets - Frauenklinik, Duesseldorf	Recruiting
Duesseldorf, Germany, D-40225
Contact: Dilloo, MD 49-211-811-7680
Universitaets - Kinderklinik - Luebeck	Recruiting
Luebeck, Germany, D-23538
Contact: Peter P. Bucsky, MD 49-451-500-2956 bucsky@paedia.ukl.mu-luebeck.de
Universitaets - Kinderklinik Wuerzburg	Recruiting
Wuerzburg, Germany, D-97080
Contact: P. G. Schlegel, MD 49-931-2010 schlegel@mail.uni-wuerzburg.de
Universitaets - Kinderklinik	Recruiting
Jena, Germany, D-07745
Contact: Felix Zintl, MD 49-3641-9300
Universitaets - Kinderklinik	Recruiting
Erlangen, Germany, 91054
Contact: W. Holter, MD 49-9131-853-3118
Universitaets - Kinderklinik	Recruiting
Jena, Germany, D-07440
Contact: Contact Peron 49-3641-938-270
Staedtisches Klinikum - Howedestrase	Recruiting
Braunschweig, Germany, 38118
Contact: Contact Person 49-531-595-1222
Universitaetskinderklinik - Universitaetsklinikum Freiburg	Recruiting
Freiburg, Germany, D-79106
Contact: Charlotte Niemeyer, MD 49-761-270-4552 charlotte.niemeyer@uniklinik-freiburg.de
Universitaets-Kinderklinik Heidelberg	Recruiting
Heidelberg, Germany, D-69120
Contact: Andreas E. Kulozik, MD, PhD 49-6221-562-311 andreas.kulozik@med.uni-heidelberg.de
Universitaets-Kinderklinik	Recruiting
Tuebingen, Germany, D-72070
Contact: Contact Person 49-707-1298-3781
Universitaetsklinikum des Saarlandes	Recruiting
Homburg, Germany, 66421
Contact: Norbert Graf 49-6841-162-4000
Universitaetsklinikum Essen	Recruiting
Essen, Germany, D-45147
Contact: Bernhard Kremens, MD 49-201-723-2453
Universitatsklinikum Carl Gustav Carus	Recruiting
Dresden, Germany, D-01307
Contact: M. Suttorp, MD 49-351-458-5035 meinolf.suttorp@uniklinikum-dresden.de
Universitaetsklinikum Halle	Recruiting
Halle, Germany, D-06097
Contact: Dieter Koerholz, MD 49-345-557-2911
Universitaetsklinikum Tuebingen	Recruiting
Tuebingen, Germany, D-72076
Contact: Rupert Handgretinger, MD 49-7071-298-3781
Universitats - Kinderklinik	Recruiting
Greiswald, Germany, 17487
Contact: James F. Beck, MD 49-3834-866-325 beck@uni-greifswald.de
Universitaetsklinikum Goettingen	Recruiting
Goettingen, Germany, D-37075
Contact: Lothar Schweigerer, MD 49-551-396-210
Universitatsklinikum der MA	Recruiting
Magdeburg, Germany, 39120
Contact: Uwe Mittler, MD 49-391-671-7210
University Hospital Schleswig-Holstein - Kiel Campus	Recruiting
Kiel, Germany, D-24105
Contact: A. Claviez, MD 49-431-597-1620 a.claviez@pediatrics.uni-kiel.de
University Medical Center Hamburg - Eppendorf	Recruiting
Hamburg, Germany, D-20246
Contact: Rudolf Erttmann, MD 49-40-428-034-270 erttmann@uke.uni-hamburg.de
University of Muenster	Recruiting
Muenster, Germany, D-48129
Contact: Contact Person 44-251-834-7742
Vestische Kinderklinik	Recruiting
Datteln, Germany, 45704
Contact: W. Andler, MD 49-2363-9750 w.andler@kinderklinik-datteln.de
Switzerland
University Children's Hospital	Recruiting
Zurich, Switzerland, CH-8032
Contact: Felix Niggli, MD 49-41-1266-7111
Kinderspital Luzern	Recruiting
Lucerne 16, Switzerland, CH-6000
Contact: U. Caflisch, MD 49-41-412-051-111
Ostschweizer Kinderspital	Recruiting
St. Gallen, Switzerland, CH-9006
Contact: Jeanette Greiner, MD 49-41-712-437-111 jeanette.greiner@kispisg.ch
Universitaets-Kinderspital beider Basel	Recruiting
Basel, Switzerland, CH-4005
Contact: Thomas Kuhne, MD 49-41-616-856-565 thomas.kuehne@ukbb.ch
Kantonspital Aarau	Recruiting
Aarau, Switzerland, CH-5001
Contact: R. Angst 49-41-628-384-941

Sponsors and Collaborators

Gesellschaft fur Padiatrische Onkologie und Hamatologie - Germany

Investigators

Study Chair:

Frank Berthold, MD

Children's Hospital

Study ID Numbers:	CDR0000517312, GPOH-NB2004, EU-20661
Study First Received:	December 11, 2006
Last Updated:	May 7, 2009
ClinicalTrials.gov Identifier:	NCT00410631 History of Changes
Health Authority:	Unspecified