N2007-01: Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma

Molecular Insight Pharmaceuticals, Inc.15 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Conditions

Neuroblastoma

Interventions

UltratraceTM Iobenguane I 131 ImagingDRUG

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.

UltratraceTM Iobenguane I 131 TherapyDRUG

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.

Eligibility

Sex: ALLMin age: 1 YearMax age: 30 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients must be at least one year and no more than 30 years of age when registered on this study. * Patients must have high risk neuroblastoma and either have tumor left after treatment started at diagnosis or have had the tumor grow back (relapsed) after getting some treatment * Patients must an MIBG scan done and it must be positive for neuroblastoma. * Patients must have a PBSC or bone marrow stem cell product available that meets study criteria. If they don't already have stem cells frozen away then they must be able to have a stem cell pheresis done to collect the necessary amount of stem cells for study entry and these stem cells must meet study criteria. * Patients must have adequate heart, lung, liver, kidney and bone marrow function. Exclusion Criteria: * They have had a stem cell transplant using another person as the stem cell donor. (You can still be in the study if a previous transplant used your own stem cells) * They have other medical problems that could get much worse if they had this treatment. * They are on dialysis for badly working kidneys or have other kidney problems. * They are pregnant or breast feeding. * They have tumor in the brain or spinal cord that is seen on a CT or MRI scan one month before starting treatment * They had total body radiation or radiation to the entire belly. * They have a known allergy to MIBG, iodine or SSKI. * They can't cooperate with the special precautions that are needed during UltratraceTM MIBG treatment or with other safety monitoring requirements of the study..

Locations (8)

Childrens Hospital Los Angeles

Los Angeles, California, United States

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Outcomes

Primary Outcomes

Maximum Tolerated Dose

The maximum tolerated dose (MTD) was defined as the dose immediately below the level at which dose escalation would be stopped due to dose limiting toxicities (DLTs). Once the MTD was reached, an additional 3 patients were to be treated at that dose level, for a total of 6 patients at that planned dose level. DLTs were defined as any of the events that are possibly, probably or definitely attributable to UltratraceTM iobenguane I 131. The MTD was supposed to be the highest dose tested at which fewer than 1/3 of pts experience a DLT when 6 patients have been treated at the MTD but the dosimetry results indicated that the maximal dosage allowed to normal organs would be exceeded if the highest planned dose (21.0 mCi/kg) was administered, so the highest dose administered in the study was 18.6 mCi/kg .

Time frame: Day 60 +/-10 or Engraftment, whichever comes first

Secondary Outcomes

Dose Limiting Toxicities

Dose limiting toxicities include treatment emergent adverse events (TEAEs) that were possibly, probably, or definitely related to Ultratrace™ Iobenguane I 131.

Time frame: From the time of signed informed consent until Day 60 or until the end of therapy evaluation is completed (whichever comes first).

Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions

The dosimetric endpoint was to estimate radiation absorbed doses to measurable lesions and to a standard set of normal organs following an imaging dose of 0.1 mCi/kg Ultratrace™ Iobenguane I 131. Biodistribution was assessed by determination of total body residence (TBR) time and by visual examination of whole body camera images. 3 timepoints were used, the 1st image was taken within 1hr after the imaging dose, the 2nd image was taken at \~24hr after imaging dose, the 3rd image was taken 2-5d after imaging dose. Whole body radiation absorbed dose estimates \& kidney, liver, and lung were calculated using the Medical Internal Radiation Dose (MIRD) schema.TBR time is derived from time integration of curve-fitted injected activity across all 3 timepoints when the isotope is emitting radiation.Three points are sampled to estimate a singular value for each organ and tissue according to the commonly used methods of the Society of Nuclear Medicine and Molecular Imaging Committee on MIRD.

Data from ClinicalTrials.gov

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