Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma

NCT00030719 | Unknown Phase 3

• 4 other identifiers: CDR0000069191SIOP-EUROPE-HR-NBL-1ESIOPEU-20148
• Study Type: interventional
• Target: 175
• Locations: 13 countries
• Sites: 32

Brief Summary

RATIONALE: Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining isotretinoin and monoclonal antibodies may kill any remaining tumor cells following surgery. It is not yet known which treatment regimen is more effective in treating neuroblastoma. PURPOSE: This randomized phase III trial is studying how well combination chemotherapy with or without filgrastim before surgery, high-dose chemotherapy, and radiation therapy followed by isotretinoin with or without monoclonal antibody work in treating patients with neuroblastoma.

Conditions

Neuroblastoma

Keywords

regional neuroblastoma; disseminated neuroblastoma; stage 4S neuroblastoma; localized unresectable neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Event-free survival at 3 years

• Mean number of febrile events during induction

Secondary Outcomes (7)

• Response rate assessed by the International Neuroblastoma Response Criteria after 4 and 8 induction chemotherapy courses

• Event-free survival at 5 years

• Overall survival

• Toxicity

• Biological factors (i.e., MycNM amplification, 1p deletion, ploidy, 17 q+, CD44, and Trk-A)

Interventions

filgrastim BIOLOGICAL

monoclonal antibody Ch14.18 BIOLOGICAL

busulfan DRUG

carboplatin DRUG

cyclophosphamide DRUG

etoposide DRUG

isotretinoin DRUG

melphalan DRUG

vincristine sulfate DRUG

bone marrow ablation with stem cell support PROCEDURE

conventional surgery PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of neuroblastoma according to International Neuroblastoma Staging System * Stage 2 or 3 with MycN amplification * Stage 4 * Tumor material available for determination of biological prognostic factors PATIENT CHARACTERISTICS: Age: * 1 to 20 at diagnosis Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Bilirubin less than 3 times normal * ALT less than 3 times normal Renal: * Creatinine less than 1.5 mg/mL * Creatinine clearance and/or glomerular filtration rate at least 60 mL/min Cardiovascular: * Shortening fraction at least 28% OR * Ejection fraction at least 55% * No clinical congestive heart failure Pulmonary: * Chest x-ray normal * Oxygen saturation normal Other: * HIV negative * No Brock grade 2 or greater * No uncontrolled infections requiring IV antivirals, antibiotics, or antifungals * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No more than 1 prior chemotherapy regimen for localized unresectable disease * No concurrent anthracyclines * No other concurrent chemotherapy Endocrine: * Not specified Radiotherapy: * Not specified Surgery: * Not specified Other: * No other concurrent investigational therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (32)

St. Anna Children's Hospital

Vienna, A-1090, Austria

RECRUITING

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

RECRUITING

Aarhus Universitetshospital - Aarhus Sygehus

Aarhus, DK-8000, Denmark

RECRUITING

Institut Gustave Roussy

Villejuif, F-94805, France

RECRUITING

Our Lady's Hospital for Sick Children Crumlin

Dublin, 12, Ireland

RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, 49202, Israel

RECRUITING

Fondazione Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Rikshospitalet University Hospital

Oslo, 0027, Norway

RECRUITING

Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA

Lisbon, 1099-023 Codex, Portugal

RECRUITING

Hospital Universitario La Fe

Valencia, 46009, Spain

RECRUITING

Karolinska University Hospital - Solna

Stockholm, S-171 76, Sweden

RECRUITING

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

RECRUITING

Birmingham Children's Hospital

Birmingham, England, B4 6NH, United Kingdom

RECRUITING

Institute of Child Health at University of Bristol

Bristol, England, BS2 8AE, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

RECRUITING

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

RECRUITING

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

RECRUITING

Royal Liverpool Children's Hospital, Alder Hey

Liverpool, England, L12 2AP, United Kingdom

RECRUITING

Middlesex Hospital

London, England, W1T 3AA, United Kingdom

RECRUITING

Great Ormond Street Hospital for Children

London, England, WC1N 3JH, United Kingdom

RECRUITING

Royal Manchester Children's Hospital

Manchester, England, M27 4HA, United Kingdom

RECRUITING

Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

RECRUITING

Queen's Medical Centre

Nottingham, England, NG7 2UH, United Kingdom

RECRUITING

Oxford Radcliffe Hospital

Oxford, England, 0X3 9DU, United Kingdom

RECRUITING

Children's Hospital - Sheffield

Sheffield, England, S10 2TH, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

RECRUITING

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

RECRUITING

Royal Belfast Hospital for Sick Children

Belfast, Northern Ireland, BT12 6BE, United Kingdom

RECRUITING

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, AB25 2ZG, United Kingdom

RECRUITING

Royal Hospital for Sick Children

Edinburgh, Scotland, EH9 1LF, United Kingdom

RECRUITING

Royal Hospital for Sick Children

Glasgow, Scotland, G3 8SJ, United Kingdom

RECRUITING

Childrens Hospital for Wales

Cardiff, Wales, CF14 4XW, United Kingdom

RECRUITING

Related Publications (2)

• Ladenstein R, Valteau-Couanet D, Brock P, Yaniv I, Castel V, Laureys G, Malis J, Papadakis V, Lacerda A, Ruud E, Kogner P, Garami M, Balwierz W, Schroeder H, Beck-Popovic M, Schreier G, Machin D, Potschger U, Pearson A. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol. 2010 Jul 20;28(21):3516-24. doi: 10.1200/JCO.2009.27.3524. Epub 2010 Jun 21.

  PMID: 20567002 RESULT

• Veal GJ, Nguyen L, Paci A, Riggi M, Amiel M, Valteau-Couanet D, Brock P, Ladenstein R, Vassal G. Busulfan pharmacokinetics following intravenous and oral dosing regimens in children receiving high-dose myeloablative chemotherapy for high-risk neuroblastoma as part of the HR-NBL-1/SIOPEN trial. Eur J Cancer. 2012 Nov;48(16):3063-72. doi: 10.1016/j.ejca.2012.05.020. Epub 2012 Jun 26.

  PMID: 22742881 DERIVED

MeSH Terms

Conditions

Neuroblastoma

Interventions

Filgrastim; dinutuximab; Busulfan; Carboplatin; Cyclophosphamide; Etoposide; Isotretinoin; Melphalan; Vincristine; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Coordination Complexes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Retinoids; Carotenoids; Polyenes; Alkenes; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ruth Ladenstein, MD

  St. Anna Kinderkrebsforschung

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 14, 2002
• First Posted: January 27, 2003
• Study Start: December 1, 2001
• Last Updated: June 24, 2014

Record last verified: 2010-08

Locations

AU (1); ES (1); IT (1); GB (20); SE (1); CH (1); BE (1); DK (1); NO (1); IE (1); IL (1); PT (1); FR (1)