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.
Radiation: UltratraceTM Iobenguane I 131 Imaging
Radiation: UltratraceTM Iobenguane I 131 Therapy
Procedure: Peripheral blood stem cell infusion
|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|
- 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.
- 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.
|Study Start Date:||March 2008|
|Study Completion Date:||November 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Radiation: UltratraceTM Iobenguane I 131 Imaging
- To establish the maximum tolerated dose of iodine I 131 metaiodobenzylguanidine (^131I-MIBG) in patients with relapsed/refractory high-risk neuroblastoma.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00659984
|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|
|Principal Investigator:||Katherine K. Matthay, MD||University of California, San Francisco|