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

NCT ID: NCT00659984

Last Updated: 2017-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-11-30

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ultratrace™ Iobenguane I 131

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.

Group Type: EXPERIMENTAL

UltratraceTM Iobenguane I 131 Imaging

Intervention Type: DRUG

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 Therapy

Intervention Type: DRUG

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.

Interventions

UltratraceTM Iobenguane I 131 Imaging

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 Type: DRUG

UltratraceTM Iobenguane I 131 Therapy

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.

Intervention Type: DRUG

Other Intervention Names

Azedra; Azedra

Eligibility Criteria

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..

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Molecular Insight Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katherine K. Matthay, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

Countries

United States

Other Identifiers

NANT-2007-01

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000593357

Identifier Type: -

Identifier Source: org_study_id