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

This study has been completed.
Sponsor:
Collaborator:
Molecular Insight Pharmaceuticals, Inc.
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier:
NCT00659984
First received: April 16, 2008
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Radiation: UltratraceTM Iobenguane I 131 Imaging
Radiation: UltratraceTM Iobenguane I 131 Therapy
Procedure: Peripheral blood stem cell infusion
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2a Study of Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by New Approaches to Neuroblastoma Therapy Consortium:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: Each patient in a Dose Level cohort must be followed until time of DLT, to day 60 +/- 10 days or until engraftment which ever comes first before escalating to the next dose level ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity (DLT) is defined as any of the events (defined in Section 4.4 of the protocol) that are (possibly, probably or definitely) attributable to UltratraceTM iobenquane I 131. The MTD will be the highest dose tested at which fewer than one third of patients experience DLT when 6 patients have been treated at the MTD. If 6 patients are treated at the highest Dose Level, 4, and fewer than 2 patients experience a DLT, then the MTD will not be reached.


Secondary Outcome Measures:
  • Toxicity [ Time Frame: From the time of signed informed consent until 60 days or until the end of therapy evaluation is completed (whichever comes first). ] [ Designated as safety issue: Yes ]
    All adverse events (AE's) observed will be summarized in terms of type (organ affected or laboratory determination), severity (by NCI CTCAE), attribution, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by Dose Level

  • Estimation of radiation absorbed doses to measurable lesions [ Time Frame: Anterior and posterior planar images will be acquired on Days 0, 1, and 2-5. ] [ Designated as safety issue: Yes ]
    Whole body radiation absorbed dose estimates and kidney, liver and lung will be calculated using the Medical Internal Radiation Dose (MIRD) schema. At least one evaluable site of tumor must be visualized on an UltratraceTM iobenguane I 131 dosimetry scan to continue on study and receive therapeutic dose UltratraceTM iobenguane I 131 on Day 0. To maximize patient safety, the dosimetry scan must show that the prescribed therapy dose will not result in > 23 Gy to the kidneys, > 30 Gy to the liver, or > 15 Gy to the lungs.

  • Objective tumor response after treatment [ Time Frame: Baseline and at day 60 +/- 10 post treatment. ] [ Designated as safety issue: No ]
    Measurable disease defined as the presence of at least one lesion that can be accurately measured in at least one dimension with the longest diameter at least 20 mm. With spiral CT scan, lesions must be at least 10 mm. Serial measurements of lesions are to be done with CT or MRI. The sum of the longest diameter (LD) for all target lesions will be calculated and reported as the disease measurement. The response of the CT/MRI lesions will be defined as outlined in section 10.1 of the protocol.

  • Quality of life [ Time Frame: At baseline and after treatment (at day 60 +/- 10 days post treatment and prior to starting non-protocol therapy). ] [ Designated as safety issue: No ]
    Patients (aged 5-18) and parents (of patients aged 2-18) will be asked to complete the 23-item Pediatric Quality of Life InventoryTM (PedsQLTM).PedsQLTM consists of 4 scales (physical, emotional, social, school functioning) which are then grouped into two summary scores and an overall summary score. Individual items, scales, and summary scores, will be summarized and reported. These descriptive analyses will provide information regarding the feasibility of these assessments as well as the magnitude of the patient-to-patient, and parent-to-parent variability.


Enrollment: 16
Study Start Date: March 2008
Study Completion Date: November 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Radiation: 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.
    Other Name: MIP-IB 13
    Radiation: UltratraceTM Iobenguane I 131 Therapy
    Therapeutic dose (per table in section 4.3.2 of protocol) 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 on this study.
    Other Name: MIP-IB 13
    Procedure: Peripheral blood stem cell infusion
    If > 12mCi/kg therapeutic dose UltratraceTM is administered, stem cells will be given day 14 +/- 3 days post -treatment. See section 4.2.3
    Other Names:
    • PBSCT
    • ABMT
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.

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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..
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659984

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States, 60637
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109-0286
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
New Approaches to Neuroblastoma Therapy Consortium
Molecular Insight Pharmaceuticals, Inc.
Investigators
Principal Investigator: Katherine K. Matthay, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier: NCT00659984     History of Changes
Other Study ID Numbers: CDR0000593357, NANT-2007-01
Study First Received: April 16, 2008
Last Updated: August 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by New Approaches to Neuroblastoma Therapy Consortium:
recurrent neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
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
3-Iodobenzylguanidine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on August 18, 2014