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NeuroblastomaPhase 2NCT00017225

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

A Phase 2 study testing filgrastim, carboplatin and cisplatin in people with Neuroblastoma, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 94 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages Up to 20 years
Conditions the study is for
Neuroblastoma
What is being tested?
filgrastim, carboplatin and cisplatin
Type of treatment
Surgery or procedure
How many people
Not given
Where
94 sitesin 3 countries
Study dates
May 1997to Feb 2002
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

94 sites in 3 countries.

94 sites in 3 countries

Germany89 sites

  • Urologische Klinik - Universitaetsklinikum Aachen

    Aachen, D-52074

  • Kinderkrankenhaus Josefinum

    Augsburg, 86154

  • Zentralklinikum Augsburg

    Augsburg, DOH-86156

  • Caritaskrankenhaus

    Bad Mergentheim, 97980

  • Klinikum Bayreuth

    Bayreuth, 95445

  • Helios Klinikum Berlin

    Berlin, 13122

  • Charite - Campus Virchow Klinikum

    Berlin, D-13353

  • Krankenanstalten Gilead

    Biefeld, 33617

  • Kinderklinik der Universitaet-Bonn

    Bonn, DOH-53113

  • Stadt Klinikum - Howedestrase

    Braunschweig, 38118

  • Zentralkrankenhaus

    Bremen, D-28205

  • Klinikum Chemnitz GMBH

    Chemnitz, D-09116

  • Klinikum Coburg

    Coburg, 96450

  • Medizinische Universitaetsklinik I

    Cologne, D-50924

  • Carl - Thiem - Klinkum Cottbus

    Cottbus, D-03048

  • Vestische Kinderklinik

    Datteln, 45704

  • Klinikum Lippe - Detmold

    Detmold, 32756

  • Stadt. Kliniken

    Dortmund, 44123

  • Stadt. KH Dresden - Neustadt

    Dresden, 01229

  • Universitatsklinikum Carl Gustav Carl Carus

    Dresden, D-01307

  • Universitaetsklinik Duesseldorf

    Düsseldorf, D-40225

  • Helios Klinikum Erfurt GmbH

    Erfurt, 99012

  • Universitaets - Kinderklinik

    Erlangen, D-91054

  • Universitaetsklinikum Essen

    Essen, D-45122

  • Klinikum der J.W. Goethe Universitaet

    Frankfurt, D-60590

  • Universitaetskinderklinik - Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Stadt. Kinderklinik

    Gelsenkirchen, 45892

  • Kinderklinik

    Giessen, D-35385

  • Universitaetsklinikum Goettingen

    Göttingen, D-37075

  • Universitats - Kinderklinik

    Greiswald, 17487

  • Kreiskrankenhaus Gummersbach GMBH

    Gummersbach, D-51643

  • St. Barbara Krankenhaus

    Halle, 06003

  • Martin Luther Universitaet

    Halle, 06097

  • Altonaer Kinderkrankenhaus

    Hamburg, 22763

  • Universitaets-Krankenhaus Eppendorf

    Hamburg, D-20246

  • Evangelische Krankenhaus Hamm

    Hamm, DOH-59063

  • Kinderkrankenhaus auf der Bult

    Hanover, 30173

  • Medizinische Hochschule Hannover

    Hanover, D-30625

  • Universitaets-Kinderklinik Heidelberg

    Heidelberg, D-69120

  • Gemeinschaftskrankenhaus

    Herdecke, 58313

  • Universitatsklinik Homburg

    Homburg, 66421

  • Marien Hospital

    Homburg, D-66421

  • Praxis am Evangelischen Krankenhaus Bethanien

    Iserlohn, D-58644

  • Universitaets - Kinderklinik

    Jena, D-07745

  • Westpfalz-Klinikum GmbH

    Kaiserslautern, D-67653

  • Stadt. Kinderklinik

    Karlsruhe, 76131

  • Kinderkrankenhaus

    Kassel, 34121

  • Klinikum Kassel

    Kassel, D-34125

  • Staedtische Krankenhaus Kiel

    Kiel, 23116

  • University Hospital Schleswig-Holstein - Kiel Campus

    Kiel, D-24105

  • Stadt. Krankenhaus Kemperhof

    Koblenz, 56065

  • Staedtisches Kinderkrankenhaus

    Koln - Riehl, D-50735

  • Klinik Konstanz

    Konstanz, 78461

  • Klinikum Krefeld GmbH

    Krefeld, D-47805

  • Universitaets - Kinderklinik

    Leipzig, 04317

  • Universitaets Klinik fuer Kinderchirurgie

    Leipzig, D-04317

  • Universitaets - Kinderklinik - Luebeck

    Lübeck, 23538

  • St. Annastift Krankenhaus

    Ludwigshafen, 67065

  • Universitatsklinikum der MA

    Magdeburg, 39112

  • Johannes Gutenberg University

    Mainz, D-55131

  • Stadt. Klinik - Kinderklinik

    Mannheim, 68167

  • Universitaets - Kinderklinik

    Marburg, 35033

  • Klinikum Minden

    Minden, D-32423

  • Universitaets - Kinderpoliklinik

    Munich, 80336

  • Kinderklinik d. TU / Schwabing

    Munich, 80804

  • Staedtisches Krankenhaus Muenchen - Harlaching

    Munich, D-81545

  • Kinderklinik

    Munich, DOH-80337

  • Klinik und Poliklinik fuer Kinderheilkunde - Universitaetsklinikum Muenster

    Münster, D-48149

  • Kinderklinik Kohlhof

    Neunkirchen, 66539

  • Cnopfche Kinderklinik

    Nuremberg, 90419

  • Klinikum Oldenburg

    Oldenburg, 26133

  • Kindershospital

    Osnabrück, D-49082

  • Krankenhaus D Barmherzigen Brueder

    Regensburg, 93049

  • Staedtische Klinikum-Kinderklinik

    Rosenheim, 83022

  • Kinderklinik - Universitaetsklinikum Rostock

    Rostock, D-18057

  • Saarbrucker Winterbergkliniken

    Saarbrücken, 66119

  • Johanniter-Kinderklinik

    Sankt Augustin, 53757

  • Diakone - Krankenhaus

    Schwäbisch Hall, 74523

  • Klinikum Schwerin

    Schwerin, D-19049

  • Leopoldina - Krankenhaus

    Schwienfurt, 97422

  • Deutsches Rotes Kreuz

    Siegen, 57072

  • Olgahospital

    Stuttgart, DOH-70176

  • Mutterhaus der Borromaerinnen

    Trier, D-54290

  • Universitaetsklinikum Tuebingen

    Tübingen, D-72076

  • Universitaet Ulm

    Ulm, D-89075

  • St. Marien Hospital

    Vechta, D-49377

  • Reinhard - Nieter - Krankenhaus

    Wilhelmshaven, 26389

  • Helios Klinikum Wuppertal

    Wuppertal, D-42283

  • Universitaets - Kinderklinik Wuerzburg

    Würzburg, D-97080

Other trials in Germany

Switzerland4 sites

  • University Children's Hospital

    Basel, CH-4005

  • Ospedale "la Carita", Locarno

    Locarno, 6600

  • Kinderspital Luzerne

    Luzerne 16, CH-6000

  • University Children's Hospital

    Zurich, CH-8032

Other trials in Switzerland

Netherlands1 site

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6202 AZ

Other trials in Netherlands

About this study

Official title: Neuroblastoma Study Phase II Study of Various Therapies in Patients With Neuroblastoma

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.

Read the 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.

Conditions
Neuroblastoma
Being tested
filgrastim, carboplatin, cisplatin, cyclophosphamide, dacarbazine
Keywords
localized resectable neuroblastoma, regional neuroblastoma, disseminated neuroblastoma, stage 4S neuroblastoma, recurrent neuroblastoma, localized unresectable neuroblastoma
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMay 1997
  3. Study completionFeb 2002

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
IDs, dates and publications
ClinicalTrials.gov ID
NCT00017225
Sponsor's protocol ID
GPOH-GERMANY-NB97
Other IDs
CDR0000068664, EU-20102, GER-GPOH-NB97
Status last verified
Aug 2002
First submitted
6 Jun 2001
Last updated
2 Aug 2013
Results posted
No

Publications

  • 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.

    PubMed 11857322

  • 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. doi: 10.1055/s-2002-33179.

    PubMed 12165893

  • 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. doi: 10.1002/gcc.10070.

    PubMed 12007190

  • 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.

    PubMed 18349403

  • 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. doi: 10.1002/pbc.21343.

    PubMed 17914735

  • 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. doi: 10.1016/s0304-3835(03)00076-4.

    PubMed 12880954

  • 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.

    PubMed 12538451

  • 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. doi: 10.1002/mpo.10313.

    PubMed 12764740

  • 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.

    PubMed 14581355

  • 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. doi: 10.1055/s-2002-36952.

    PubMed 12548494

  • Simon T, Hero B, Bongartz R, Schmidt M, Muller 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. doi: 10.1007/s00066-006-1498-8.

    PubMed 16826357

  • Kremens B, Hero B, Esser J, Weinel P, Filger-Brillinger J, Fleischhack G, Graf N, Gruttner 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 Immunol Immunother. 2002 Apr;51(2):107-10. doi: 10.1007/s00262-001-0259-x. Epub 2002 Feb 1.

    PubMed 11904735

  • Decarolis B, Simon T, Krug B, Leuschner I, Vokuhl C, Kaatsch P, von Schweinitz D, Klingebiel T, Mueller I, Schweigerer L, Berthold F, Hero B. Treatment and outcome of Ganglioneuroma and Ganglioneuroblastoma intermixed. BMC Cancer. 2016 Jul 27;16:542. doi: 10.1186/s12885-016-2513-9.

    PubMed 27465021

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing filgrastim, carboplatin and cisplatin in people with Neuroblastoma, run by German Society for Pediatric Oncology and Hematology GPOH gGmbH at 94 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 94 sites in Germany, Switzerland, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00017225, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.

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