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Completed

NCT Number: NCT00659984

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

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.

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Key information

Conditions

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

Age range

1 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Childrens Hospital Los Angeles, Los Angeles, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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..

Treatment and study plan

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.

Other names: Azedra

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.

Other names: Azedra

Primary outcomes

  1. Maximum Tolerated Dose

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

    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 .

Secondary outcomes

  1. Dose Limiting Toxicities

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

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

  2. Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions

    Time frame: Day 5 post Dosimetric Dose

    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.

  3. Overall Objective Tumor Response Post Therapeutic Treatment

    Time frame: Day 60 +/- 10 days post Therapeutic Dose

    The International Neuroblastoma Response Criteria (INRC) were utilized as a basis for the overall response criteria, which incorporated responses in MIBG positive lesions,bone marrow disease, and CT/MRI lesions that met NANT-modified RECIST criteria. Efficacy success was defined as the proportion of pts who were successful overall [i.e., achieving a Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR)] determined by independent reviewers. CR = Disappearance of all target lesions, homovanillic acid/ vanillylmandelic acid (HVA/VMA) normal (NL); VGPR = > 90% decr of disease for CT/MRI target lesions, all pre-existing bone lesions with CR by MIBG; MIBG scan can be SD/CR in soft tissue lesions. CR in bone marrow, no new tumor sites, and NL HVA/VMA.; PR = At least 30% decr in disease measurement for CT/MRI target lesions. Bone marrow with CR, MIBG with either PR/CR in bone lesions, MIBG may be SD /CR in soft tissue lesions, and HVA/VMA may still be elevated.

  4. Tumor Response in CT/MRI Lesions Post Therapeutic Treatment

    Time frame: Day 60 +/- 10 days post Therapeutic Dose

    Measurable disease was defined for a conventional CT scan by the presence of at least one lesion that could be accurately measured in at least one dimension with the longest diameter at least 20 mm by Independent Review. Efficacy success was defined as a patient achieving a Complete Response (CR)=disappearance of all target and non-target CT/MRI lesions; or, Very Good Partial Response (VGPR)=greater than 90% decrease of the disease measurement for CT/MRI lesions, taking as reference the disease measurement done to confirm measurement disease at study entry. Non-target CT/MRI lesions stable to smaller in size; or, Partial Response (PR)=at least 30% decrease in the disease measurement for CT/MRI lesions, taking as reference the disease measurement done to confirm measurable disease at study entry. Non-target CT/MRI lesions stable to smaller in size.

  5. Quality of Life

    Time frame: Day 60 +/- 10 days post Therapeutic Dose

    Patients (aged 5-18) and parents (of patients aged 2-18) were 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 averaged into an overall summary score (scale: 0-100 with 0 representing the worst possible Quality of Life overall summary score and 100 representing the best possible Quality of Life overall summary score). The mean difference between the post treatment overall summary score and the baseline overall summary score is reported.

Sponsors and collaborators

Lead sponsor

Molecular Insight Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 2a Study of Ultratrace™ Iobenguane I 131 in Patients With Relapsed/Refractory High-Risk Neuroblastoma

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
Apr 17, 2008
Registry last updated
Oct 4, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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