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
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|ClinicalTrials.gov Identifier: NCT01175356|
Recruitment Status : Completed
First Posted : August 4, 2010
Results First Posted : September 28, 2017
Last Update Posted : November 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Disseminated Neuroblastoma Ganglioneuroblastoma Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Regional Neuroblastoma Stage 4S Neuroblastoma||Drug: cyclophosphamide Drug: topotecan hydrochloride Drug: cisplatin Drug: etoposide phosphate Drug: vincristine sulfate Drug: doxorubicin hydrochloride Radiation: iobenguane I 131 Procedure: therapeutic conventional surgery Drug: busulfan Drug: melphalan 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 Drug: isotretinoin Other: pharmacological study Other: questionnaire administration Other: laboratory biomarker analysis||Not Applicable|
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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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||99 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||September 28, 2016|
|Actual Study Completion Date :||September 28, 2016|
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
- Percentage of MIBG Avid Patients Treated With Meta-iodobenxylguanide (MIBG) Labeled With Iodine-131 [ Time Frame: Up to 6 weeks after course 5 of induction ]Number of MIBG avid patients who receive 131I-MIBG divided by the number of patients evaluable for the feasibility of MIBG endpoint x 100%.
- Percentage of MIBG Avid Patients Treated With MIBG Labeled With Iodine-131 and Bu/Mel Chemotherapy [ Time Frame: Up to day -6 of conditioning ]Number of MIBG avid patients who receive 131I-MIBG and Bu/Mel divided by the number of patients evaluable for the feasibility of MIBG and Bu/Mel consolidation endpoint x 100%.
- 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 [ Time Frame: Up to 6 weeks after course 5 of induction ]Number of patients who had an unacceptable toxicity or experienced SOS. Unacceptable toxicity was defined as CTC Grade 4-5 Pulmonary/Respiratory.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01175356
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|Principal Investigator:||Brian Weiss, MD||Children's Oncology Group|