Neoplasms

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Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

3-Iodobenzylguanidine

Enzyme Inhibitors

Radiopharmaceuticals

131I-MIBG Therapeutic Administration. Therapeutic 131I-MIBG will be synthesized at Jubilant DraxImage (Quebec, Canada) with specific activities of 9-18 Ci/mmole, or at Progenics with specific activity of 2,500 mCi/mg. The therapeutic dose (8-18 mCi/kg at investigator's discretion; any dose greater than 12 requires stored stem cells) will be diluted in 25-50 ml of normal saline for either preparation, and will be infused intravenously through a patient's central line, if already present, or a peripheral IV if a central line is not present.If Azedra is used, the dose will be infused over 30-60 minutes; the low specific activity preparation from Draximage will be infused over 90-120 minutes. For patients with pheochromocytoma or paraganglioma, the recommended maximum dose is 500 mCI or 12 mCi/kg.

Metaiodobenzylguanidine (MIBG)

Emily Theobald

Kieuhoa Vo, MD

This is a compassionate use protocol to allow patients with advanced neuroblastoma palliative access to 131I-metaiodobenzylguanidine (131I-MIBG).

Neuroblastoma remains a fatal disease for a large percentage of patients, especially those with high-risk disease features who become resistant to conventional therapy. 131I-metaiodobenzylguanidine (131I-MIBG) is a norepinephrine analog that concentrates in adrenergic tissue and therefore holds promise for cell-specific treatment of neuroblastoma. 131I-MIBG is active against relapsed or refractory neuroblastoma and associated hematopoietic toxicity can be abrogated with autologous stem cell rescue. 131I-MIBG given in doses of 10-18 millicurie (mCi)/kg with stem cell rescue, if necessary, is safe and effective palliative therapy for refractory or relapsed neuroblastoma patients.

131I-Labeled MIBG for Refractory Neuroblastoma: A Compassionate Use Protocol

Cannonball Kids' Cancer Foundation

Kieuhoa Vo

Principal Investigator

Irinotecan

Vincristine

The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG.

The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG.

Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.

Steven DuBois, M.D.

This is a pilot study to determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a one week schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

131I-metaiodobenzylguanidine (131I-MIBG) is an active therapy in patients with widely metastatic, treatment-resistant neuroblastoma, where response rates are 20-40% at doses (\> 15mCi/kg) requiring stem cell rescue. Irinotecan is a topoisomerase I inhibitor with single-agent chemotherapeutic activity against neuroblastoma and other pediatric solid tumors in phase I and II clinical trials. With more protracted schedules (e.g. daily for 5 days/week x 2 weeks), the major dose-limiting toxicity is diarrhea. With shorter schedules, myelosuppression becomes dose-limiting. In adult solid tumors, irinotecan has been an effective radiosensitizer and is currently being evaluated by the Children's Oncology Group for this purpose in rhabdomyosarcoma protocols incorporating external beam radiotherapy.

Compared to single-agent 131I-MIBG, the combination of topotecan (a related camptothecin) and 131I-MIBG demonstrated superior pre-clinical activity in mouse xenograft models of neuroblastoma. This combination had no unexpected toxicities in a pilot clinical study. We have completed a clinical trial of vincristine, irinotecan, 131I-MIBG that utilized irinotecan on a protracted schedule (5 days per week x 2 weeks). The rationale for this schedule was to provide a greater degree of overlap between the radiation sensitizer (irinotecan) and the radiation exposure provided following 131I-MIBG infusion. This combination was shown to be tolerable at doses up to 18 mCi/kg 131I-MIBG. However, more patients experienced grade 2 and 3 diarrhea than would be customary with the dose and schedule of irinotecan used in that trial. It is therefore of interest to determine whether this combination of irinotecan, vincristine, and 131I-MIBG will be better tolerated using irinotecan at higher doses in a shorter schedule. The current standard schedule in Children's Oncology Group protocols for the combination of vincristine, irinotecan is now a higher dose in five, rather than 10 days. In the current pilot study, we will evaluate the tolerability and anti-tumor activity of this combination using irinotecan given once daily for 5 days only. Two 131I-MIBG dose levels will be evaluated. This study will provide the basis for a future randomized trial.

High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma

Pilot Study of High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed High-Risk Neuroblastoma

To determine whether doses of 15 mCi/kg and 18 mCi/kg of 131I-MIBG are tolerable when given with irinotecan/vincristine on a 5-day schedule to children and young adults with high-risk refractory/relapsed neuroblastoma.

Therapeutic response rate to regimen according to the NANT modified-version of the International Neuroblastoma Response Criteria.

Rate of protocol associated diarrhea according to UGT1A1 genotype.

To describe changes in standardized uptake values (SUVs) obtained by 18FDG-PET scan at study entry and in response to one cycle of protocol therapy.

Thrasher Research Fund

University of California, San Francisco

Assistant Professor of Pediatrics

The first cohort for safety will be 3-6 patients treated with vincristine and irinotecan and 15 mCi/kg of 131I-MIBG.

Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.

15 mCi/kg of 131I-MIBG

The second cohort will be 3-6 patients at the same doses of vincristine and irinotecan and 18 mCi/kg of 131I-MIBG.

Metaiodobenzylguanidine (MIBG): Chemotherapy will be given over 5 days for each course, with a single dose of 131I-MIBG on the second day of irinotecan. A total course will be defined as 42 days, or longer if hematopoietic recovery to eligibility criteria occurs after day 42.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
131I-Labeled MIBG for Refractory Neuroblastoma: A Compassionate Use Protocol	NCT01370330	Neuroblastoma	Metaiodobenzylg...	1 Year -	University of California, San Francisco
High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma	NCT01313936	Neuroblastoma	Metaiodobenzylg...	1 Year - 30 Years	University of California, San Francisco
High-Dose 131I-MIBG Therapy Combined With Vincristine and Five Days of Irinotecan for Resistant/Relapsed Neuroblastoma	NCT01313936	Neuroblastoma	Metaiodobenzylg...	1 Year - 30 Years	University of California, San Francisco

Spots Global Cancer Trial Database for metaiodobenzylguanidine (mibg)