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
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Stage 4S Neuroblastoma
Drug: topotecan hydrochloride
Drug: etoposide phosphate
Drug: vincristine sulfate
Drug: doxorubicin hydrochloride
Radiation: iobenguane I 131
Procedure: therapeutic conventional surgery
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: 3-dimensional conformal radiation therapy
Radiation: external beam radiation therapy
Radiation: intensity-modulated radiation therapy
Other: pharmacological study
Other: questionnaire administration
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A COG Pilot Study of Intensive Induction Chemotherapy and 131I-MIBG Followed by Myeloablative Busulfan/Melphalan (Bu/Mel) for Newly Diagnosed High-Risk Neuroblastoma|
- Proportion of MIBG avid patients who are able to be treated with iobenguane I 131 [ Time Frame: Up to 6 weeks after course 5 of induction ] [ Designated as safety issue: No ]This proportion will be calculated as the number of MIBG avid patients who receive iobenguane I 131 divided by the number of patients evaluable for the feasibility of MIBG endpoint. The definition of receive iobenguane I 131 is receiving iobenguane I 131.
- Proportion of MIBG avid patients who are able to be treated with iobenguane I 131 and then Bu/Mel [ Time Frame: Day -6 of conditioning ] [ Designated as safety issue: No ]This proportion will be calculated as the number of MIBG avid patients who receive iobenguane I 131 and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint. The definition of receiving Bu/Mel conditioning is receiving the first dose of planned Busulfan on Day -6 of conditioning.
- Percentage of average per capita income encompassed by the total of travel + housing + lost wages [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]Patient/caregiver surveys will provide the information about travel for each patient. Cost of travel for each person will be determined using standard mileage reimbursement rates. Standard federal per diem rates will be utilized for families who stay in a hotel. Lost wages will be calculated for up to a maximum of 2 adults. In order to determine if the 'out-of-pocket' costs are less than 10% of yearly income, expenditures will be totaled and compared to the average per capita income, assuming 52-weeks with a 40-hour work week.
- Proportion of eligible high-risk patients accrued to the study [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
- Event-free survival rate [ Time Frame: Time from enrollment to the first occurrence of relapse, progression, secondary malignancy or death, assessed at 1 year ] [ Designated as safety issue: No ]A 95% confidence interval will be calculated for the 1-year EFS rate. Will perform a comparison of the 1-year EFS rate on this study versus a hypothesized model of the standard using the methodology of Woolson.
- Response rate, defined as the proportion of evaluable patients who attain a response of partial response or better at the end of iobenguane I 131 + Bu/Mel therapy and local radiotherapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]Response will be determined using the International Response Criteria.
- Incidence of adverse events and SOS, assessed by Common Terminology Criteria version 4.0 for toxicity assessment and grading [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2010|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (131I-MIBG, chemotherapy)
See Detailed Description.
Other Names:Drug: topotecan hydrochloride
Other Names:Drug: cisplatin
Other Names:Drug: etoposide phosphate
Other Names:Drug: vincristine sulfate
Other Names:Drug: doxorubicin hydrochloride
Other Names:Radiation: iobenguane I 131
Other Names:Procedure: therapeutic conventional surgery
Undergo surgeryDrug: busulfan
Other Names:Drug: melphalan
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantationProcedure: in vitro-treated peripheral blood stem cell transplantation
Undergo autologous in vitro-treated peripheral blood stem cell transplantation
Other Names:Radiation: 3-dimensional conformal radiation therapy
Other Names:Radiation: external beam radiation therapy
Other Name: EBRTRadiation: intensity-modulated radiation therapy
Other Name: IMRTDrug: isotretinoin
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: questionnaire administration
Ancillary studiesOther: laboratory biomarker analysis
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I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131]) delivered after multi-agent chemotherapy, and b) post-induction busulfan/melphalan (Bu/Mel) consolidation therapy.
I. To assess the tolerability of treating high-risk neuroblastoma patients, age 365 days - 30 years, with a) an induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-induction Bu/Mel consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy.
I. To assess the response rate after a regimen of induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy.
II. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response.
III. To assess the relative reliability of 123 I-MIBG and fludeoxyglucose F-18 (18FDG)-positron emission tomography (PET) imaging in assessment of tumor activity at diagnosis, and prior to surgical resection.
IV. To compare detectable tumor burden on the pre-surgical resection radioiodinated-MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan.
V. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG.
VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and relate exposure to SOS incidence.
INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.
Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2.
Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5.
Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3.
Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive iobenguane I 131 IV over 90-120 minutes on day 1.
SURGERY: Patients undergo surgery after course 4 or before consolidation therapy.
CONSOLIDATION THERAPY: Within 10-12 weeks from the date of iobenguane I 131 infusion, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1.
AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0.
RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2 dimensional [D], 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease.
MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01175356
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|Principal Investigator:||Brian Weiss, MD||Children's Oncology Group|