COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Therapy Based on Stage of Disease and Risk Assessment in Treating Children With Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002802
Recruitment Status : Completed
First Posted : May 12, 2004
Last Update Posted : December 19, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which treatment regimen is most effective in treating patients with different stages of and risk factors for neuroblastoma.

PURPOSE: Phase III trial to study the effectiveness of therapy based on stage of disease and risk assessment in treating children with neuroblastoma.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: dacarbazine Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: melphalan Drug: mesna Drug: vincristine sulfate Drug: vindesine Procedure: autologous bone marrow transplantation Procedure: conventional surgery Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy Radiation: radioisotope therapy Phase 3

Detailed Description:

OBJECTIVES: I. Increase the survival rates and duration of survival in children and adolescents with neuroblastoma by using stage- and risk group-appropriate therapy. II. Determine whether using cisplatin/etoposide/vindesine and vincristine/dacarbazine/ifosfamide/doxorubicin instead of cisplatin/teniposide and vincristine/dacarbazine/cyclophosphamide/doxorubicin improves remission rate and lessens toxicity in patients with stage 3C, 3D, or 4 neuroblastoma. III. Determine whether local radiotherapy to the primary tumor and bone metastasis improves local tumor control in these patients. IV. Compare the efficacy and survival associated with short-term, high-dose conditioning chemotherapy plus autologous bone marrow transplantation vs. long-term, low-dose cytostatic chemotherapy as consolidation therapy in these patients. V. Determine whether early use of low-dose doxorubicin/vincristine plus hepatic irradiation slows disease progression in patients with stage 4S-C neuroblastoma. VI. Determine whether 4 courses of chemotherapy reduces the occurrence of local and systemic relapse in patients with stages 2, 3A, and 3B neuroblastoma. VII. Determine whether serum tumor markers (LDH, catecholamine metabolites, and neuron-specific enolase) are predictive of remission behavior.

OUTLINE: Patients are staged according to the International Neuroblastoma Staging System and are further defined by progressively less favorable risk groups based on age at diagnosis, serum LDH, and tumor resectability (risk groups A, B, C, and D, representing presence of 0, 1, 2, or 3 risk factors, respectively). Patients who are unable to be resected at entry or with incomplete resection are re-evaluated at 4-month intervals for the appropriateness of tumor resection. STAGE 1 PATIENTS Patients undergo complete primary tumor resection and no other therapy. STAGES 2, 3A, AND 3B PATIENTS Patients undergo primary tumor resection, followed by cisplatin, etoposide, vindesine (PEV) alternating monthly with vincristine, dacarbazine, ifosfamide, doxorubicin (VDIA). Patients in complete remission (CR) discontinue therapy, while those with less than CR receive additional therapy as outlined below for stages 3C, 3D, and 4 patients, except that these patients are not eligible for bone marrow transplantation. STAGES 3C, 3D, AND 4 PATIENTS Patients receive PEV and VDIA as above, with radiotherapy to sites of metastases during the third and fourth courses, following which autologous bone marrow is collected. Following marrow harvest, patients receive up to 4 more alternating courses of PEV/VDIA; those with no response or progressive disease after the sixth chemotherapy course are referred for other therapy. Patients who complete PEV/VDIA receive 3 weeks of radiotherapy to the primary tumor bed or residual tumor. Stage 4 patients in complete or very good partial remission and with sufficient harvested marrow undergo ABMT following radiotherapy. Myeloablation consists of high-dose MIBG radioisotope therapy followed by high-dose melphalan, etoposide, and carboplatin. All other patients and those who refuse ABMT receive 1 year of alternating, low-dose chemotherapy courses, beginning concurrently with initiation of radiotherapy. One regimen consists of oral melphalan/etoposide for 5 days and the other regimen consists of intravenous vincristine on 1 day and oral cyclophosphamide for 7 days. Therapy continues for 1 year. STAGE 4S PATIENTS Patients in risk groups 4S-A and 4S-B receive no therapy. Patients in group 4S-C receive 4-8 weekly injections of doxorubicin and vincristine (AV). Patients with tumor progression may receive low-dose radiotherapy. Primary tumor resection may be delayed up to 8 months after diagnosis in these patients. Use of G-CSF is allowed but not recommended.

PROJECTED ACCRUAL: Approximately 500 patients will be accrued on this multicenter study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Non-Randomized
Primary Purpose: Treatment
Study Start Date : July 1990
Actual Study Completion Date : September 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

DISEASE CHARACTERISTICS: Neuroblastoma with diagnosis based on one of the following: Histologic confirmation Cytologic confirmation in bone marrow and elevated catecholamine metabolites Typical tumor appearance on CT, MRI, or ultrasound and: Unequivocal MIBG uptake in tumor Elevated catecholamines in serum or urine No primitive neuroectodermal tumor or primary intracerebral neuroblastoma Such patients referred to protocol GER-HIT90

PATIENT CHARACTERISTICS: Age: Under 21 Other: No serious cerebral trouble No severe concomitant disease, e.g.: No severe congenital malformation No severe organ function abnormality

PRIOR CONCURRENT THERAPY: No prior cytostatic therapy (e.g., for Wilms' tumor) No concurrent therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002802

Layout table for location information
University of Cologne
Frechen, Germany, DOH-5-0226
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Layout table for investigator information
Study Chair: Frank Berthold, MD Children's Hospital Medical Center, Cincinnati
Publications of Results:
Other Publications:
Layout table for additonal information Identifier: NCT00002802    
Other Study ID Numbers: CDR0000064902
First Posted: May 12, 2004    Key Record Dates
Last Update Posted: December 19, 2013
Last Verified: May 2007
Keywords provided by National Cancer Institute (NCI):
localized resectable neuroblastoma
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
localized unresectable neuroblastoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Liposomal doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists