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

NCT00659984 | Completed Phase 2 Results DMC

• 2 other identifiers: CDR0000593357NANT-2007-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

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.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (1)

• 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 .

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

Secondary Outcomes (5)

• Dose Limiting Toxicities

  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

  Day 5 post Dosimetric Dose

• Overall Objective Tumor Response Post Therapeutic Treatment

  Day 60 +/- 10 days post Therapeutic Dose

• Tumor Response in CT/MRI Lesions Post Therapeutic Treatment

  Day 60 +/- 10 days post Therapeutic Dose

• Quality of Life

  Day 60 +/- 10 days post Therapeutic Dose

Study Arms (1)

Ultratrace™ Iobenguane I 131

EXPERIMENTAL

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.

Drug: UltratraceTM Iobenguane I 131 Imaging; Drug: UltratraceTM Iobenguane I 131 Therapy

Interventions

UltratraceTM Iobenguane I 131 Imaging 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.

Also known as: Azedra

Ultratrace™ Iobenguane I 131

UltratraceTM Iobenguane I 131 Therapy 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.

Also known as: Azedra

Ultratrace™ Iobenguane I 131

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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..

Sponsors & Collaborators

• Molecular Insight Pharmaceuticals, Inc.: lead

Study Sites (8)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

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

Ann Arbor, Michigan, 48109-0286, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: NANT Operations Center
• Organization: NANT Consortium

nantops@chla.usc.edu

323-361-5687

Study Officials

• Katherine K. Matthay, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Ultratrace™ Iobenguane I 131

Study Record Dates

• First Submitted: April 16, 2008
• First Posted: April 17, 2008
• Study Start: June 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: November 1, 2010
• Last Updated: October 4, 2017
• Results First Posted: March 16, 2017

Record last verified: 2017-09

Locations

US (8)