Clinical trial NCT00659984
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
Sponsor: Molecular Insight Pharmaceuticals, Inc.
Start date: 2008-06-01; Completion date: 2010-11-01
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIBG), may carry radiation directly to tumor cells and not harm normal cells. A bone marrow or peripheral stem cell transplant using stem cells from the patient may be able to replace blood-forming cells that were destroyed by I 131 MIBG.

PURPOSE: This phase II trial is studying the side effects and best dose of iodine I 131 MIBG followed by a stem cell transplant in treating young patients with relapsed or refractory high-risk neuroblastoma.

Detailed description:
OBJECTIVES:

Primary

* To establish the maximum tolerated dose of iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) in patients with relapsed/refractory high-risk neuroblastoma.

Secondary

* To describe toxicity following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following a 0.1 mCi/kg \[3.7 MBq/kg\] (minimum dose of 1.0 mCi \[37 MBq\] but not to exceed 5.0 mCi \[185 MBq\]) intravenous administration of \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To describe, within the confines of a phase IIa trial, objective tumor response following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To explore dose-response following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.
* To explore quality of life assessment following treatment with \^131I-MIBG in patients with relapsed/refractory high-risk neuroblastoma.

OUTLINE:

* Dosimetry: Patients receive a dosimetric dose of iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) IV over 1-3 minutes. Patients then undergo 2 or 3 MIBG scans within 5 days of the dosimetry dose to assess biodistribution and tumor uptake. Patients with normal tumor uptake and biodistribution proceed to treatment.
* Treatment: Within 1-4 weeks of the dosimetric dose, patients with normal tumor uptake and biodistribution receive a therapeutic dose of \^131I-MIBG IV over 1 hour on day 0 and undergo MIBG scan on day 7. Patients then proceed to autologous stem cell infusion.
* Autologous stem cell infusion: Patients receive an infusion of autologous stem cells from peripheral blood or bone marrow on day 14. Patients with an ANC of \< 500/µl at any point after autologous stem cell infusion receive filgrastim (G-CSF) IV or subcutaneously once daily until ANC is \> 2,000/µl.

Patients complete a quality of life questionnaire at baseline and then at day 60.

After completion of study treatment, patients are followed at day 60 and periodically thereafter.

Arms: arm 1: Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 (1-5 mCi) within 7 days of study enrollment, followed by three dosimetry scans over 3-6 days. If the imaging dose demonstrated normal biodistribution and tumor uptake, then the patient received a therapeutic dose within 7-28 days of the diagnostic imaging dose, followed by a single imaging scan on Day 7 post therapy. As per protocol, therapeutic dosing was to begin at 12.0 mCi/kg and escalate to 15.0, 18.0, and 21.0 mCi/kg until the MTD was established or the 21.0 mCi/kg dose level was reached. Actual doses administered ranged from 8.8 to 18.6 mCi/kg. Based on actual doses administered, patients were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.

The dosimetry dose was administered over a period of 1-3 minutes by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused intravenously over 30 to 60 minutes.
Interventions: intervention 1: UltratraceTM Iobenguane I 131 Imaging intervention 2: UltratraceTM Iobenguane I 131 Therapy
Intervention descriptions: intervention 1: 0.1 mCi/kg \[3.7 MBq/kg\] (minimum dose 1mCi \[37MBq\] but not to exceed 5 mCi \[185 MBq\]) of UltratraceTM Iobenguane I 131 given 7 -28 days before therapeutic dose administration on day 0. Thyroid protection will be administered per institutional protocol for I-131-MIBG however, thyroid blocking must be started prior to the Ultratrace imaging dose. Anterior and posterior whole body images will be taken to assess organ distribution, tumor uptake and dosimetry calculations. intervention 2: Therapeutic dose will be given on Day 0 if dosimetry scans showed that the prescribed or adjusted dose will not exceed \> 23 Gy to the kidneys, \> 30 Gy to the liver, or \> 15 Gy to the lungs. and tumor uptake confirmed with UltratraceTM imaging dose. Only one treatment course of therapeutic UltratraceTM will be given in this study.

Protocol documents: