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Trial record 46 of 531 for:    "Neuroblastoma"

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

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ClinicalTrials.gov Identifier: NCT00659984
Recruitment Status : Completed
First Posted : April 17, 2008
Results First Posted : March 16, 2017
Last Update Posted : October 4, 2017
Sponsor:
Information provided by (Responsible Party):
Molecular Insight Pharmaceuticals, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neuroblastoma
Interventions Drug: UltratraceTM Iobenguane I 131 Imaging
Drug: UltratraceTM Iobenguane I 131 Therapy
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description

Eligible patients received a diagnostic imaging dose of Ultratrace™ Iobenguane I 131 within 7 days (d) of enrollment, followed by 3 dosimetry scans over 3-6 days. For the imaging dose, 0.1 mCi/kg (3.7 MBq/kg), at a min dose of 1 mCi (37 MBq) but not to exceed 5 mCi (185 MBq) of Ultratrace™ Iobenguane I 131 was administered 7-28 d prior to the therapeutic dose on Day 0. If the imaging dose demonstrated NL biodistribution/tumor uptake, pts received a therapeutic dose within 7-28 d of the imaging dose followed by a single imaging scan on Day 7 post therapy.

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. Based on actual doses administered, pts were grouped into 3 mean dose groups: 11.2, 15.5, and 18.2 mCi/kg.

The dosimetry dose was administered over 1-3 mins by injection; the therapeutic dose was diluted in up to 25 mL normal saline and infused over 30 to 60 mins.

Period Title: Overall Study
Started 15
Completed 14
Not Completed 1
Reason Not Completed
Adverse Event             1
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description 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. Therapeutic dosing began at 12.0 mCi/kg and escalated 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. 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.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 15 participants
8
(3 to 30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
6
  40.0%
Male
9
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
1.Primary Outcome
Title Maximum Tolerated Dose
Hide Description 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 .
Time Frame Day 60 +/-10 or Engraftment, whichever comes first
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection) and all 15 patients later received a single therapeutic dose of Ultratrace™ Iobenguane I 131.
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description:
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient’s dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: mCi/kg
18.6
2.Secondary Outcome
Title Dose Limiting Toxicities
Hide Description Dose limiting toxicities include treatment emergent adverse events (TEAEs) that were possibly, probably, or definitely related to Ultratrace™ Iobenguane I 131.
Time Frame From the time of signed informed consent until Day 60 or until the end of therapy evaluation is completed (whichever comes first).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection) and all 15 patients later received a single therapeutic dose of Ultratrace™ Iobenguane I 131.
Arm/Group Title 11.2 mCi Group 15.5 mCi Group 18.2 mCi Group
Hide Arm/Group Description:
11.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
15.5 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
18.2 mCi/kg Ultratrace™ Iobenguane I 131 represents the mean dose administered to this group of subjects.
Overall Number of Participants Analyzed 6 3 6
Measure Type: Number
Unit of Measure: number of DLTs
0 0 0
3.Secondary Outcome
Title Dosimetric Estimation of Radiation Absorbed Doses to Measurable Lesions
Hide Description 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.
Time Frame Day 5 post Dosimetric Dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 15 patients underwent dosimetry (received a single imaging dose of Ultratrace™ Iobenguane I 131 injection).
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description:
Following therapeutic dosing at the 12.0, 15.0, and 18.0 mCi/kg cohorts, 4 patients who were to receive the 21.0 mCi/kg therapeutic dose were required to have their planned dose reduced below the dose that was calculated based on the patient’s dosimetry results, in order to meet the protocol guidelines for maximal dosage allowed to normal organs described above. Because of the differences between the planned and actual therapeutic doses that were administered to several patients, patients were grouped and the study data were presented and analyzed by actual doses rather than by the planned dose cohorts of 12.0, 15.0, 18.0, and 21.0 mCi/kg. Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: Gy
Kidney 16.7  (5.2)
Liver 12.7  (4.1)
Lungs 11.1  (2.8)
4.Secondary Outcome
Title Overall Objective Tumor Response Post Therapeutic Treatment
Hide Description 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.
Time Frame Day 60 +/- 10 days post Therapeutic Dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The evaluable population (which excludes non-evaluable responses) contains one patient less than the full ITT population.
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description:
The proportion of patients who were considered successful defined as a patient achieving a Complete Response, Very Good Partial Response or Partial Response as determined by the Independent Reviewers.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of evaluable population
0.29
(0.01 to 0.56)
5.Secondary Outcome
Title Tumor Response in CT/MRI Lesions Post Therapeutic Treatment
Hide Description 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.
Time Frame Day 60 +/- 10 days post Therapeutic Dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The evaluable population (which excludes non-evaluable responses) contains one patient less than the full ITT population.
Arm/Group Title Over Tumor Response
Hide Arm/Group Description:
The proportion of patients who were considered successful defined as a patient achieving a Complete Response, Very Good Partial Response or Partial Response as determined by the Independent Reviewers.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of evaluable population
21
(0 to 46)
6.Secondary Outcome
Title Quality of Life
Hide Description 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.
Time Frame Day 60 +/- 10 days post Therapeutic Dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Self reported PedsQL™ scores were obtained for 9 patients in the ITT population (n=15) at baseline (prior to the start of the Ultratrace™ Iobenguane I 131 imaging studies) and at the end of therapy (60 ±10 days post treatment).
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description:
Based on the actual doses administered, patients were grouped into 3 dose groups of 6, 3, and 6 patients, according to the mean doses of the groups, which were 11.2, 15.5, and 18.2 mCi/kg, respectively.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.2  (11.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ultratrace™ Iobenguane I 131
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.363
Comments [Not Specified]
Method Cochran Armitage Trend Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
-3.4 to 13.9
Estimation Comments [Not Specified]
Time Frame From the time of signed informed consent until Day or until the end of therapy evaluation was completed (whichever occurred first).
Adverse Event Reporting Description Serious adverse events (SAEs) that were ongoing at study completion (Day 60 ±10 days) were followed for 60 days or until resolution, whichever occurred first.
 
Arm/Group Title Ultratrace™ Iobenguane I 131
Hide Arm/Group Description 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. Mean therapeutic dosing groups were 11.2 mCi/kg, 15.5 nCi/kg 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.
All-Cause Mortality
Ultratrace™ Iobenguane I 131
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ultratrace™ Iobenguane I 131
Affected / at Risk (%) # Events
Total   5/15 (33.33%)    
Blood and lymphatic system disorders   
Febrile neutropenia  2/15 (13.33%)  2
General disorders   
Disease progression  1/15 (6.67%)  1
Infections and infestations   
Upper respiratory tract infection  1/15 (6.67%)  1
Infection  1/15 (6.67%)  1
Bacteremia  1/15 (6.67%)  1
Neutropenia infection  1/15 (6.67%)  1
1
Term from vocabulary, MedDRA (11.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Ultratrace™ Iobenguane I 131
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Blood and lymphatic system disorders   
Leukopenia  15/15 (100.00%) 
Thrombocytopenia  15/15 (100.00%) 
Neutropenia  14/15 (93.33%) 
Lymphopenia  8/15 (53.33%) 
Febrile Neutropenia  2/15 (13.33%) 
Gastrointestinal disorders   
Nausea  9/15 (60.00%) 
Vomiting  6/15 (40.00%) 
Diarrhoea  4/15 (26.67%) 
Salivary gland pain  4/15 (26.67%) 
Salivary gland enlargement  3/15 (20.00%) 
Abdominal pain  2/15 (13.33%) 
Constipation  2/15 (13.33%) 
Dry mouth  2/15 (13.33%) 
General disorders   
Pyrexia  5/15 (33.33%) 
Fatigue  3/15 (20.00%) 
Oedema peripheral  2/15 (13.33%) 
Infections and infestations   
Candidiasis  2/15 (13.33%) 
Investigations   
Aspartate aminotransferase increased  12/15 (80.00%) 
Hemoglobin decreased  11/15 (73.33%) 
Alanine aminotransferase increased  9/15 (60.00%) 
Activated partial thromboplastin time prolonged  3/15 (20.00%) 
Blood bilirubin increased  3/15 (20.00%) 
Weight decreased  3/15 (20.00%) 
Metabolism and nutrition disorders   
Anorexia  4/15 (26.67%) 
Hypokalaemia  3/15 (20.00%) 
Hyponatraemia  3/15 (20.00%) 
Hyperglycaemia  2/15 (13.33%) 
Hypocalcaemia  2/15 (13.33%) 
Hypoglycaemia  2/15 (13.33%) 
Hypophosphataemia  2/15 (13.33%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  2/15 (13.33%) 
Neck pain  2/15 (13.33%) 
Pain in jaw  2/15 (13.33%) 
Nervous system disorders   
Headache  4/15 (26.67%) 
Dysgeusia  2/15 (13.33%) 
Renal and urinary disorders   
Bladder spasm  2/15 (13.33%) 
Respiratory, thoracic and mediastinal disorders   
Nasal congestion  2/15 (13.33%) 
Skin and subcutaneous tissue disorders   
Alopecia  2/15 (13.33%) 
Vascular disorders   
Hypertension  2/15 (13.33%) 
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: NANT Operations Center
Organization: NANT Consortium
Phone: 323-361-5687
Responsible Party: Molecular Insight Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00659984     History of Changes
Other Study ID Numbers: CDR0000593357
NANT-2007-01 ( Other Identifier: NANT Consortium )
First Submitted: April 16, 2008
First Posted: April 17, 2008
Results First Submitted: December 15, 2015
Results First Posted: March 16, 2017
Last Update Posted: October 4, 2017