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
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.
Localized Resectable Neuroblastoma
Localized Unresectable Neuroblastoma
Drug: doxorubicin hydrochloride
Other: pharmacological study
Other: questionnaire administration
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Radiation: external beam radiation therapy
Radiation: intensity-modulated radiation therapy
Drug: topotecan hydrochloride
Drug: etoposide phosphate
Drug: vincristine sulfate
Radiation: meta-iodobenzylguanidine (MIBG) labeled with iodine-131
|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 treated with meta-iodobenzylguanidine (MIBG) labeled with iodine-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 MIBG labeled with iodine-131 divided by the number of patients evaluable for the feasibility of MIBG endpoint. The definition of receive MIBG labeled with iodine-131 is receiving MIBG labeled with iodine-131.
- Proportion of MIBG avid patients treated with MIBG labeled with iodine-131 and Bu/Mel chemotherapy [ 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 MIBG labeled with iodine-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.
- Incidence of adverse events and SOS, assessed by Common Terminology Criteria (CTC)v.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: MIBG labeled with iodine-131/isotretinoin/vincristine
See Detailed Description
Drug: doxorubicin hydrochloride
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: questionnaire administration
Ancillary studiesProcedure: 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:Procedure: therapeutic conventional surgery
Undergo surgeryRadiation: 3-dimensional conformal radiation therapy
Other Names:Radiation: external beam radiation therapy
Other Name: EBRTRadiation: intensity-modulated radiation therapy
Other Name: IMRTDrug: cyclophosphamide
Other Names:Drug: topotecan hydrochloride
Other Names:Drug: cisplatin
Other Names:Drug: etoposide phosphate
Other Names:Drug: vincristine sulfate
Other Names:Radiation: meta-iodobenzylguanidine (MIBG) labeled with iodine-131
Other Names:Drug: busulfan
Other Names:Drug: melphalan
Other Names:Drug: isotretinoin
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I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days to 30 years, with an induction block of meta-iodobenzylguanidine (MIBG) labeled with iodine-131 delivered after multi-agent chemotherapy, and post-Induction busulfan/melphalan (Bu/Mel) consolidation therapy.
I. To assess the tolerability of these regimens in these patients, age 365 days - 30 years, with a) an Induction block of meta-iodobenzylguanidine labeled with iodine-131 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 meta-iodobenzylguanidine (MIBG) labeled with iodine-131 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 18FDG-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 meta-iodobenzylguanidine labeled with iodine-131 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 MIBG labeled with iodine-131.
VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and to relate exposure to SOS incidence.
OUTLINE: This is a pilot, multicenter study.
INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.
Course 1: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 for 3 weeks of weeks 1-3.
Course 2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5 for 3 weeks/21 days of weeks 4-6. Patients undergo peripheral blood stem cell (PBSC) collection.
Course 3: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3 for 3 weeks/21 days of weeks 7-9.
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 for 3 weeks/21 days of weeks 10-12. Patients undergo surgery to remove remaining tumor following course 4.
Course 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3 for 3 weeks/21 days of weeks 13-15.
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 MIBG labeled with iodine-131 induction therapy beginning 3-6 weeks after course 5.
SURGERY: Patients undergo surgery after course 4 or before consolidation therapy.
CONSOLIDATION THERAPY: Within 4-6 weeks after completion of induction therapy, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. Patients also complete a questionnaire regarding costs for travel and accommodations during therapy. Blood samples maybe collected after the first dose of busulfan for pharmacokinetic assays.
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 (2D, 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|