Trial Outcomes & Findings for A Phase I/II Study of [124I]mIBG PET/CT in Neuroblastoma (NCT NCT02043899)
NCT ID: NCT02043899
Last Updated: 2021-06-21
Results Overview
Analysis of \[124I\]mIBG PET/CT and \[123I\]mIBG planar scintigraphy was performed retrospectively by four specialist observers. The analysis was performed and observers were blinded to each others scores. The observers subsequently reviewed the lesions identified and, where there was a difference in their separate scores, they returned to the images in order to reach an agreed consensus score. The number of lesions identified as positive by this consensus scoring (all lesions with a SIOPEN score of 4 or 5) were used to meet the primary objective.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
36 participants
Primary outcome timeframe
[124I]mIBG PET/CT imaging on Day 1, three to 21 days after routine [123I]mIBG imaging and before the start of any new anti-cancer therapy. A minimum interval of 72 hours was required between injection of [123I]mIBG tracer and the [124I]mIBG PET/CT scan.
Results posted on
2021-06-21
Participant Flow
Trial participants were enrolled at two trial sites between 11 February 2014 and 10 September 2019.
Participant milestones
| Measure |
Single Arm Trial
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Overall Study
STARTED
|
36
|
|
Overall Study
Underwent Routine [123I]mIBG Planar and SPECT/CT Imaging
|
32
|
|
Overall Study
Underwent [124I]mIBG PET/CT Imaging
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
Single Arm Trial
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Failure to meet the clinical criteria for [124I]mIBG imaging
|
5
|
|
Overall Study
Technical manufacturing issue or logistical difficulties of [123I]mIBG or [124I]mIBG supply
|
12
|
|
Overall Study
Temporary halt due to out of specification radioactivity
|
2
|
|
Overall Study
Clinical progression necessitating urgent treatment
|
1
|
|
Overall Study
Treatment delayed
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Single Arm Trial
n=36 Participants
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Age, Categorical
<=18 years
|
24 Participants
n=36 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=36 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=36 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=36 Participants
|
|
Region of Enrollment
United Kingdom
|
36 participants
n=36 Participants
|
PRIMARY outcome
Timeframe: [124I]mIBG PET/CT imaging on Day 1, three to 21 days after routine [123I]mIBG imaging and before the start of any new anti-cancer therapy. A minimum interval of 72 hours was required between injection of [123I]mIBG tracer and the [124I]mIBG PET/CT scan.Population: All patients who received both \[123I\]mIBG and \[124I\]mIBG
Analysis of \[124I\]mIBG PET/CT and \[123I\]mIBG planar scintigraphy was performed retrospectively by four specialist observers. The analysis was performed and observers were blinded to each others scores. The observers subsequently reviewed the lesions identified and, where there was a difference in their separate scores, they returned to the images in order to reach an agreed consensus score. The number of lesions identified as positive by this consensus scoring (all lesions with a SIOPEN score of 4 or 5) were used to meet the primary objective.
Outcome measures
| Measure |
Single Arm Trial
n=9 Participants
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG Planar Scintigraphy Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive lesions observed using [124I]mIBG PET/CT
|
714 Lesions
|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG Planar Scintigraphy Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive lesions observed using [123I]mIBG planar scintigraphy
|
405 Lesions
|
SECONDARY outcome
Timeframe: [124I]mIBG PET/CT imaging on Day 1, three to 21 days after routine [123I]mIBG imaging and before the start of any new anti-cancer therapy. A minimum interval of 72 hours was required between injection of [123I]mIBG tracer and the [124I]mIBG PET/CT scan.Population: All patients who received both \[123I\]mIBG and \[124I\]mIBG
Analysis of \[124I\]mIBG PET/CT and \[123I\]mIBG SPECT/CT was performed retrospectively by four specialist observers. The analysis was performed and observers were blinded to each others scores. The observers subsequently reviewed the lesions identified and, where there was a difference in their separate scores, they returned to the images in order to reach an agreed consensus score. The number of lesions identified as positive by this consensus scoring (all lesions with a SIOPEN score of 4 or 5) were used to meet the primary objective.
Outcome measures
| Measure |
Single Arm Trial
n=9 Participants
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive skeletal lesions observed using [124I]mIBG PET/CT
|
421 Lesions
|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive skeletal lesions observed using [123I]mIBG SPECT/CT
|
249 Lesions
|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive soft tissue lesions observed using [124I]mIBG PET/CT
|
132 Lesions
|
|
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
Number of positive soft tissue lesions observed using [123I]mIBG SPECT/CT
|
64 Lesions
|
SECONDARY outcome
Timeframe: Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.Documenting Adverse Events (AEs), Serious Adverse Events (SAEs), Dose Limiting Toxicities (DLTs) (Graded According to NCI-CTCAE Version 4.02) and Laboratory Parameters and Determining Their Causality in Relation to \[123I\]mIBG and \[124I\]mIBG.
Outcome measures
| Measure |
Single Arm Trial
n=32 Participants
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
All AEs
|
25 Events
|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
Pretreatment AEs (occurring before [123I]mIBG administration)
|
16 Events
|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
Treatment Emergent AEs (occurring following [123I]mIBG administration)
|
9 Events
|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
SAEs
|
3 Events
|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
[123I]mIBG Related AEs
|
0 Events
|
|
Determining the Causality of Each Adverse Event to [124I]mIBG and Grading Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.02.
[124I]mIBG Related AEs
|
0 Events
|
Adverse Events
Single Arm Trial
Serious events: 2 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Single Arm Trial
n=32 participants at risk
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
General disorders
Fever
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
Other adverse events
| Measure |
Single Arm Trial
n=32 participants at risk
\[124I\]meta-Iodobenzylguanidine: Single intravenous administration of \[124I\]mIBG Solution for Injection on Day 1 with a maximum radioactive dose of 1.42 MBq/kg (±10%) and a maximum injected dose of 50 MBq \[124I\]mIBG equating to a maximum chemical dose of 10 micrograms of stable mIBG. The activity to paediatric patients will be scaled by weight based upon the EANM paediatric dose card (Lassmann et al., 2007). This will result in an activity between 10 MBq and 50 MBq depending on the patient's weight.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
9.4%
3/32 • Number of events 3 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Ear and labyrinth disorders
Ear Pain
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Constipation
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Diarrhea
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
4/32 • Number of events 4 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Oral pain
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Gastrointestinal disorders
Vomiting
|
9.4%
3/32 • Number of events 3 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
General disorders
Fever
|
6.2%
2/32 • Number of events 2 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Infections and infestations
Mucosal infection
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Infections and infestations
Upper respiratory infection
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Metabolism and nutrition disorders
Anorexia
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
3.1%
1/32 • Number of events 1 • Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
|
Additional Information
Regulatory Affairs Manager
Cancer Research UK Centre for Drug Development
Phone: +44 203 4696878
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place