Disseminated Neuroblastoma | Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin
Disseminated Neuroblastoma research study
What is the primary objective of this study?
This clinical trial is studying induction therapy followed by meta-iodobenzylguanidine (MIBG) labeled with iodine-131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as MIBG labeled with iodine-131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as cisplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant can replace blood-forming cells that are damaged by MIBG labeled with iodine-131 and chemotherapy.
Who is eligible to participate?
Inclusion Criteria: - Patients have a diagnosis of neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria: - Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging System (INSS) stage 4 are eligible with the following: - v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of additional biologic features - Age > 18 months (> 547 days) regardless of biologic features - Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or deoxyribonucleic acid [DNA] index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown - Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the following: - MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features - Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status - Patients with newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features - Patients >= 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to stage 4 for INSS stage 1, 2, 4S - Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life-threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per low- or intermediate-risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age and/or gender as follows: - 0.6 mg/dL (1 to < 2 years of age) - 0.8 mg/dL (2 to < 6 years of age) - 1.0 mg/dL (6 to < 10 years of age) - 1.2 mg/dL (10 to < 13 years of age) - 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age) - 1.7 mg/dL (male) or 1.4 mg/dL (female) ( >= 16 years of age) - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN for age - Shortening fraction >= 27% by echocardiogram or - Ejection fraction >= 50% by radionuclide evaluation - No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure - All patients and/or their parents or legal guardians must sign a written informed consent - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: - Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method - Female patients who are lactating must agree to stop breast-feeding - Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible - Patients are not eligible if they have received local radiation which includes any of the following: 1200 centigray (cGy) to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Stage 4S Neuroblastoma
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:topotecan hydrochlorideGiven IV
Drug:etoposide phosphateGiven IV
Drug:vincristine sulfateGiven IV
Drug:doxorubicin hydrochlorideGiven IV
Radiation:iobenguane I 131Given IV
Procedure:therapeutic conventional surgeryUndergo surgery
Procedure:autologous hematopoietic stem cell transplantationUndergo autologous in vitro-treated peripheral blood stem cell transplantation
Procedure:in vitro-treated peripheral blood stem cell transplantationUndergo autologous in vitro-treated peripheral blood stem cell transplantation
Radiation:3-dimensional conformal radiation therapyUndergo radiotherapy
Radiation:external beam radiation therapyUndergo radiotherapy
Radiation:intensity-modulated radiation therapyUndergo radiotherapy
Other:pharmacological studyCorrelative studies
Other:questionnaire administrationAncillary studies
Other:laboratory biomarker analysisCorrelative studies
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Treatment (131I-MIBG, chemotherapy)See Detailed Description.
Start Date: October 2010
Completed Date: September 28, 2016
Primary Outcome: Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131
Secondary Outcome: Incidence of Unacceptable Toxicity and Sinusoidal Obstruction Syndrome (SOS), Assessed by Common Terminology Criteria (CTV)v.4.0 for Toxicity Assessment and Grading for I-MIBG
Study sponsors, principal investigator, and references
Principal Investigator: Brian Weiss, MD
Lead Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)