Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-Risk Neuroblastoma

NCT ID: NCT00526318

Last Updated: 2015-07-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Brief Summary

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RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of tumor cells by stopping them from dividing or by killing them. It also prepares the patient's bone marrow for the stem cell transplant. The stem cells are given to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving isotretinoin after transplant may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given before a stem cell transplant and isotretinoin in treating neuroblastoma.

PURPOSE: This randomized clinical trial is studying two different combination chemotherapy regimens to compare how well they work when given before a stem cell transplant and isotretinoin in treating young patients with high-risk neuroblastoma.

Detailed Description

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OBJECTIVES:

Primary

* Compare the event-free survival of pediatric patients with high-risk neuroblastoma treated with standard induction chemotherapy vs topotecan hydrochloride-containing induction chemotherapy followed by myeloablative autologous stem cell transplantation and consolidation therapy with isotretinoin.

Secondary

* Compare the overall survival of patients treated with these regimens.
* Compare early response (complete response, very good partial response, partial response, mixed response, stable disease, and progression/relapse) after 2 courses of standard vs experimental induction chemotherapy (or after 60 days if the second course is not yet finished).
* Compare response to standard vs experimental induction chemotherapy before autologous stem cell transplantation (or after 280 days if induction chemotherapy is not yet finished).
* Compare the toxicity of standard vs experimental induction chemotherapy during courses 1 and 2 and the frequency of ≥ grade 3 toxicity during the last 6 courses of induction chemotherapy.
* Compare the extent of initial surgery and best surgery (biopsy vs incomplete resection vs macroscopic complete resection) and the frequency of complications related to surgery (e.g., nephrectomy, bleeding, infection, or intestinal obstruction).
* Compare the acute and long-term side effects of external-beam radiotherapy.
* Correlate the activity of MIBG and whole-body radiation dose.
* Collect and store tumor material in the tumor bank for future evaluation of other molecular markers (MYCN and status of chromosome 1p and 11q) and prognostic significant gene signatures.

OUTLINE: This is a multicenter study. Patients are stratified according to disease stage, lactate dehydrogenase (LDH) status, MYCN status, and age at diagnosis (stage 4 disease; LDH not elevated; any MYCN status; age at diagnosis 1-21 years vs stage 4 disease; LDH elevated; any MYCN status; age at diagnosis ≥ 1 but \< 2 years vs stage 4 disease; LDH elevated; any MYCN status; age at diagnosis 2-21 years vs localized disease; MYCN amplification; age at diagnosis ≥ 6 months)

* Induction chemotherapy: Patients are randomized to 1 of 2 induction chemotherapy arms.

* Arm I (standard): Patients receive N5 chemotherapy comprising cisplatin IV continuously over 96 hours and etoposide phosphate IV continuously over 96 hours on days 1-4 and vindesine IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 9 and continuing until blood counts recover. Patients then receive N6 chemotherapy comprising vincristine IV over 1 hour on days 1 and 8, dacarbazine IV over 1 hour on days 1-5, ifosfamide IV continuously over 120 hours on days 1-5, and doxorubicin hydrochloride IV over 4 hours on days 6 and 7. Patients also receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recover. Treatment with N5 and N6 chemotherapy alternates every 21 days for 6 courses (N5 chemotherapy is given in courses 1, 3, and 5 and N6 chemotherapy is given in courses 2, 4, and 6).
* Arm II (experimental): Patients receive N8 chemotherapy comprising cyclophosphamide IV over 1 hour on days 1-7, topotecan hydrochloride IV continuously over 168 hours on days 1-7, and etoposide phosphate IV over 1 hour on days 8-10. Patients also receive G-CSF SC once daily beginning on day 12 and continuing until blood counts recover. Treatment with N8 chemotherapy repeats every 21 days for 2 courses. Patients then receive N5 chemotherapy alternating with N6 chemotherapy as in arm I.
* Surgery: Patients may undergo secondary surgery after completion of 4 or 6 courses of induction chemotherapy but prior to radiotherapy.
* Radiotherapy (131I-MIBG therapy and external-beam radiotherapy \[EBRT\]): Patients with active residual primary tumor after the completion of induction chemotherapy undergo \^131I-MIBG therapy\* prior to autologous stem cell transplantation (ASCT) and EBRT after ASCT.

NOTE: \*Patients with MIBG negative neuroblastoma at initial diagnosis will only receive EBRT.

* Myeloablative ASCT: Patients receive melphalan IV over 30 minutes on days -8 to -5, etoposide phosphate IV over 4 hours on day -4, and carboplatin IV over 1 hour on days -4 to -2. Patients undergo reinfusion of CD34+ stem cells on day 0. Patients also receive G-CSF SC or IV over 4 hours once daily beginning on day 2 and continuing until blood counts recover.
* Consolidation therapy (isotretinoin)\*: Beginning 30 days after ASCT, patients receive oral isotretinoin once daily on days 1-14. Treatment repeats every 28 days for up to 6 courses. Beginning 3 months later, patients receive an additional 3 courses of isotretinoin.

NOTE: \*Isotretinoin must not be given concurrently with radiotherapy

After completion of study treatment, patients are followed every 6 weeks for 1 year, every 3 months for 4 years, and then every 6 months thereafter.

Conditions

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Neuroblastoma

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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filgrastim

Intervention Type BIOLOGICAL

carboplatin

Intervention Type DRUG

cisplatin

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

dacarbazine

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

etoposide phosphate

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

isotretinoin

Intervention Type DRUG

melphalan

Intervention Type DRUG

topotecan hydrochloride

Intervention Type DRUG

vincristine sulfate

Intervention Type DRUG

vindesine

Intervention Type DRUG

autologous hematopoietic stem cell transplantation

Intervention Type PROCEDURE

iobenguane I 131

Intervention Type RADIATION

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Diagnosis of neuroblastoma according to any of the following criteria:

* Histological diagnosis from tumor tissue
* Presence of distinct neuroblastoma cells in the bone marrow and elevated catecholamine metabolites (HVA, VMA) in blood or urine
* High-risk disease, meeting 1 of the following criteria:

* Stage 4 disease, regardless of the MYCN status (1-21 years of age)
* Stage 1-3 or 4S disease with MYCN amplification (6 months -21 years of age)

PATIENT CHARACTERISTICS:

* Not pregnant or nursing
* Fertile patients must use effective contraception (hormonal contraception or intra-uterine device \[IUD\])

PRIOR CONCURRENT THERAPY:

* No concurrent participation in another clinical trial that would preclude the interventions or outcome assessment of this clinical trial
* No other concurrent anticancer therapy
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German Society for Pediatric Oncology and Hematology GPOH gGmbH

OTHER

Sponsor Role lead

Principal Investigators

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Frank Berthold, MD

Role: STUDY_CHAIR

Children's Hospital Medical Center, Cincinnati

Locations

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Kinderklinik - Universitaetsklinikum Aachen

Aachen, , Germany

Site Status RECRUITING

Klinikum Augsburg

Augsburg, , Germany

Site Status RECRUITING

Klinikum Bayreuth

Bayreuth, , Germany

Site Status RECRUITING

Helios Klinikum Berlin

Berlin, , Germany

Site Status RECRUITING

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

Site Status RECRUITING

Evangelisches Krankenhauus Bielfeld

Biefeld, , Germany

Site Status RECRUITING

Kinderklinik der Universitaet Bonn

Bonn, , Germany

Site Status RECRUITING

Staedtisches Klinikum - Howedestrase

Braunschweig, , Germany

Site Status RECRUITING

Klinikum Bremen-Mitte

Bremen, , Germany

Site Status RECRUITING

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Site Status RECRUITING

Klinikum Coburg

Coburg, , Germany

Site Status RECRUITING

Children's Hospital

Cologne, , Germany

Site Status RECRUITING

Carl - Thiem - Klinkum Cottbus

Cottbus, , Germany

Site Status RECRUITING

Vestische Kinderklinik

Datteln, , Germany

Site Status RECRUITING

Klinikum Lippe - Detmold

Detmold, , Germany

Site Status RECRUITING

Klinikum Dortmund

Dortmund, , Germany

Site Status RECRUITING

Universitatsklinikum Carl Gustav Carus

Dresden, , Germany

Site Status RECRUITING

Klinikum Duisburg

Duisburg, , Germany

Site Status RECRUITING

Universitaetsklinikum Duesseldorf

Düsseldorf, , Germany

Site Status RECRUITING

Helios Klinikum Erfurt

Erfurt, , Germany

Site Status RECRUITING

Universitaets - Kinderklinik

Erlangen, , Germany

Site Status RECRUITING

Universitaetsklinikum Essen

Essen, , Germany

Site Status RECRUITING

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Site Status RECRUITING

Universitaetskinderklinik - Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Kinderklinik

Giessen, , Germany

Site Status RECRUITING

Universitaetsklinikum Goettingen

Göttingen, , Germany

Site Status RECRUITING

Universitats - Kinderklinik

Greiswald, , Germany

Site Status RECRUITING

Universitaetsklinikum Halle

Halle, , Germany

Site Status RECRUITING

Krankenhaus St. Elisabeth und St. Barbara

Halle, , Germany

Site Status RECRUITING

University Medical Center Hamburg - Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status RECRUITING

Universitaets-Kinderklinik Heidelberg

Heidelberg, , Germany

Site Status RECRUITING

Gemeinschaftskrankenhaus

Herdecke, , Germany

Site Status RECRUITING

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Site Status RECRUITING

Universitaets - Kinderklinik

Jena, , Germany

Site Status RECRUITING

Staedtisches Klinikum Karlsruhe gGmbH

Karlsruhe, , Germany

Site Status RECRUITING

Klinikum Kassel

Kassel, , Germany

Site Status RECRUITING

University Hospital Schleswig-Holstein - Kiel Campus

Kiel, , Germany

Site Status RECRUITING

Klinikum Kemperhof Koblenz

Koblenz, , Germany

Site Status RECRUITING

Klinikum Krefeld GmbH

Krefeld, , Germany

Site Status RECRUITING

St. Annastift Krankenhaus

Ludwigshafen, , Germany

Site Status RECRUITING

Universitaets - Kinderklinik - Luebeck

Lübeck, , Germany

Site Status RECRUITING

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, , Germany

Site Status RECRUITING

Johannes Gutenberg University

Mainz, , Germany

Site Status RECRUITING

Staedtisches Klinik - Kinderklinik

Mannheim, , Germany

Site Status RECRUITING

Universitaetsklinikum Giessen und Marburg GmbH - Marburg

Marburg, , Germany

Site Status RECRUITING

Klinikum Minden

Minden, , Germany

Site Status RECRUITING

Krankenhaus Muenchen Schwabing

Munich, , Germany

Site Status RECRUITING

Dr. von Haunersches Kinderspital der Universitaet Muenchen

Munich, , Germany

Site Status RECRUITING

Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster

Münster, , Germany

Site Status RECRUITING

Klinikum Neubrandenburg

Neubrandenburg, , Germany

Site Status RECRUITING

Cnopf'sche Kinderklinik

Nuremberg, , Germany

Site Status RECRUITING

Klinikum Oldenburg

Oldenburg, , Germany

Site Status RECRUITING

Klinik St. Hedwig-Kinderklinik

Regensburg, , Germany

Site Status RECRUITING

Kinderklinik - Universitaetsklinikum Rostock

Rostock, , Germany

Site Status RECRUITING

Johanniter-Kinderklinik

Sankt Augustin, , Germany

Site Status RECRUITING

Kinderklink Siegen Deutsches Rotes Kreuz

Siegen, , Germany

Site Status RECRUITING

Olgahospital

Stuttgart, , Germany

Site Status RECRUITING

Krankenanstalt Mutterhaus der Borromaerinnen

Trier, , Germany

Site Status RECRUITING

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Site Status RECRUITING

Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Ulm, , Germany

Site Status RECRUITING

Helios Kliniken Wuppertal University Hospital

Wuppertal, , Germany

Site Status RECRUITING

Universitaets - Kinderklinik Wuerzburg

Würzburg, , Germany

Site Status RECRUITING

Kantonsspital Aarau

Aarau, , Switzerland

Site Status RECRUITING

Universitaets-Kinderspital beider Basel

Basel, , Switzerland

Site Status RECRUITING

Kinderspital Luzern

Lucerne, , Switzerland

Site Status RECRUITING

Ostschweizer Kinderspital

Sankt Gallen, , Switzerland

Site Status RECRUITING

University Children's Hospital

Zurich, , Switzerland

Site Status RECRUITING

Countries

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Germany Switzerland

Facility Contacts

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R. Mertens, MD, PhD

Role: primary

49-241-808-9902

Astrid Gnekow

Role: primary

49-821-400-3603

T. Rupprecht

Role: primary

49-921-400-1400

Lothar Schweigerer, MD

Role: primary

49-30-9401-2345

Gunter Henze

Role: primary

49-30-450-660-31

N. Jorch, MD

Role: primary

49-52-177-278-050

Udo Bode, MD

Role: primary

49-228-2873-3215

Wolfgang Eberl, MD

Role: primary

49-531-595-1222

Arnulf Pekrun, MD, PhD

Role: primary

49-421-497-3656

Krause, MD

Role: primary

49-371-3332-4124

Roland Frank, MD

Role: primary

49-9561-22-5547

Frank Berthold, MD

Role: primary

49-221-478-4380

D Mobius, MD

Role: primary

49-355-462336

W. Andler, MD

Role: primary

49-023-63-9750

Klaus Wesseler, MD

Role: primary

49-523-172-4511

Dominik T. Schneider, MD

Role: primary

49-231-953-2-1670

M. Suttorp, MD

Role: primary

49-351-458-0

Ruef, MD

Role: primary

49-203-733-2421

Arndt Borkhardt

Role: primary

49-211-311-7990

Axel Sauerbrey, MD

Role: primary

49-361-781-3729

W. Holter, MD

Role: primary

49-9131-853-3118

Bernhard Kremens, MD

Role: primary

49-201-723-2453

Thomas Klingebiel, MD

Role: primary

49-69-6301-5094

Charlotte Niemeyer, MD

Role: primary

49-761-270-4506

Alfred Reiter, MD

Role: primary

49-641-994-3420

M. Lakomek, MD

Role: primary

49-551-398-600

James F. Beck, MD

Role: primary

49-383-486-6325

Dieter Koerholz, MD

Role: primary

49-345-557-2387

G. Guenther, MD

Role: primary

49-345-482-50

Rudolf Erttmann, MD

Role: primary

49-40-4717-4270

Karl Welte, MD

Role: primary

49-511-532-6710

Andreas E. Kulozik, MD, PhD

Role: primary

49-6221-564-555

Christoph Tautz, MD

Role: primary

49-2330-62-3914

Norbert Graf

Role: primary

49-6841-162-4000

Felix Zintl, MD

Role: primary

49-3641-938-270

A. Leipold

Role: primary

49-721-974-3311

Martina Rodehueser, MD

Role: primary

49-561-980-3066

A. Claviez, MD

Role: primary

49-431-597-1622

M. Rister, MD

Role: primary

49-261-499-2602

S. Volpel, MD

Role: primary

49-2151-32-2375

Barbara Selle, MD

Role: primary

49-621-5702-4449

Peter P. Bucsky, MD

Role: primary

49-451-500-2956

P. Vorwerk, MD

Role: primary

49-394-672-791

P. Gutjahr, MD

Role: primary

49-6131-17-2112

M. Duerken

Role: primary

49-621-383-2243

H. Christiansen, MD

Role: primary

49-6421-286-2671

Bernhard Erdlenbruch, MD

Role: primary

49-57-1801-4601

Stefan Burdach, MD, PhD

Role: primary

49-89-3068-2352

Irene Schmid, MD

Role: primary

49-89-5160-7978

Heribert F. Juergens, MD

Role: primary

49-251-834-7742

H. J. Feickert, MD, PhD

Role: primary

49-395-775-2901

W. Scheurlen

Role: primary

49-911-334-002

Hermann Mueller, MD

Role: primary

49-441-403-2013

Ove Peters

Role: primary

49-941-369-5404

Carl Friedrich Classen, MD, PD

Role: primary

49-381-494-0

Roswitha Dickerhoff, MD

Role: primary

49-22-41-2491

Rainer Burghard, MD

Role: primary

49-271-2345-0

Stefan Bielack, MD

Role: primary

49-711-99-24-61

Wolfgang Rauh, MD

Role: primary

49-651-947-2654

Rupert Handgretinger, MD

Role: primary

49-7071-298-2087

Klaus M. Debatin, MD

Role: primary

49-731-5002-7790

K. Sinha, MD

Role: primary

49-202-896-2441

P. G. Schlegel, MD

Role: primary

49-931-201-27-831

R. Angst

Role: primary

41-62-838-4906

Thomas Kuhne, MD

Role: primary

41-61-685-6565

U. Caflisch, MD

Role: primary

41-41-205-11-11

Jeanette Greiner, MD

Role: primary

41-71-243-13-60

Felix Niggli, MD

Role: primary

41-44-266-7823

Other Identifiers

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CDR0000564820

Identifier Type: REGISTRY

Identifier Source: secondary_id

UNI-KOELN-161

Identifier Type: -

Identifier Source: secondary_id

EU-20661

Identifier Type: -

Identifier Source: secondary_id

GPOH-NB2004-HR

Identifier Type: -

Identifier Source: org_study_id

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