Metastatic NeuroblastomaPhase 1/2NCT02043899
A Phase I/II Study of [124I]mIBG PET/CT in Neuroblastoma
A Phase 1/2 study testing [124I]meta-Iodobenzylguanidine in people with Metastatic Neuroblastoma, run by Cancer Research UK at 2 sites in United Kingdom.
Trial summary
This study aims to show that 3-dimensional PET/CT imaging with a new novel PET tracer (called [124I]mIBG) can detect as many or more sites of neuroblastoma (a type of childhood cancer) compared to the recommended 1-dimensional routine scans (called [123I]mIBG planar scintigraphy). Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Metastatic Neuroblastoma
- What is being tested?
- [124I]meta-Iodobenzylguanidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Feb 2014to 15 Oct 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically proven Stage 4 neuroblastoma as defined by the International Neuroblastoma Staging System (INSS).
- Aged ≥ 1 year at the time that written informed consent is given.
- Planned to undergo conventional [123I]mIBG planar scintigraphy for routine clinical care of neuroblastoma.
- Life expectancy of at least 12 weeks.
- World Health Organisation (WHO) performance status of 0, 1 or 2 for patients aged > 12 years old or Lansky play scale score of ≥ 50% for patients aged ≤ 12 years old.
- Written (signed and dated) informed consent from patient ≥ 16 years old and/or parent or legal guardian for patients <16 years old and the patient be capable of co-operating with scanning requirements. (N.B. Written or verbal assent as appropriate should be sought from all patients who are under 16 years old).
Who cannot join
- Treatment with any medications contra-indicated with mIBG scanning as listed in Appendix 4 of the trial protocol. For example, decongestants containing pseudoephedrine, phenylpropalomine and phenylephrine, sympathomimetics, cocaine, antihypertensives, tricyclic antidepressants. These drugs should be stopped before administration as indicated in this list (usually for four biological half-lives to allow almost complete wash-out but refer to list).
- Stage 4S neuroblastoma as defined by the INSS.
- Any anti-cancer treatment planned between the routine [123I]mIBG imaging and the [124I]mIBG PET/CT scan on Day 2. Anti-cancer treatments can be started only after the Off-Study assessment on Day 3 to Day 7, see schedule of assessments in Section 7. N.B. Patients should not be enrolled in the study if their participation will delay their subsequent treatment for neuroblastoma.
- Female patients who are pregnant or lactating.
- At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
- Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
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- Patients with known hypersensitivity to mIBG.
- Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.
- Clinical Criteria for [124I]mIBG imaging
- One or more disease foci observed on conventional [123I]mIBG planar scintigraphy. Disease foci will initially be identified by a Nuclear Medicine physician at the investigational site.
- ≥ 3kg at the time of the [124I]mIBG imaging to agree with the paediatric EANM guidelines.
- Haematological and biochemical indices within the ranges below:
- For patients ≤16 years old, haematological and biochemical indices within the following ranges: Haemoglobin ≥ 7.0 g/dl (N.B transfusions will be allowed); Absolute neutrophil count ≥ 0.2 x 10^9/L (N.B. G-CSF support will be allowed); Platelet count ≥ 10 x 10^9/L (N.B. transfusions will be allowed); Serum bilirubin ≤ 2.5 x upper limit of normal (ULN); Alanine amino-transferase (ALT), aspartate amino-transferase (AST), and/ or alkaline phosphatase (ALP) ≤ 5 x ULN; and Calculated creatinine clearance using revised Schwartz formula ≥ 60 mL/min/1.73m^2.
- For patients >16 years old, haematological and biochemical indices within the following ranges: Haemoglobin ≥ 8.0 g/dl (N.B transfusions will be allowed); Absolute neutrophil count ≥ 0.5 x 10^9/L (N.B. G-CSF support will be allowed); Platelet count ≥ 50 x 10^9/L (N.B. transfusions will be allowed); Serum bilirubin ≤ 2.5 x upper limit of normal (ULN); Alanine amino-transferase (ALT), aspartate amino-transferase (AST), and/ or alkaline phosphatase (ALP) ≤ 5 x ULN; and Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73m^2.
- Menarchal female patients must have a negative serum or urine pregnancy test before administration of [124I]mIBG Solution for Injection on Day 1 and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) to be effective from Day 1 and for 7 days afterwards.
- Male patients with partners of child-bearing potential must agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] from Day 1 and for 7 days afterwards. Male patients with pregnant or lactating partners must agree to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University College London Hospital
London, NW1 2PG
Royal Marsden Hospital
Sutton, SM2 5PT
About this study
Official title: A Cancer Research UK Phase I/II Study to Compare [124I]Meta-Iodobenzylguanidine (mIBG) Positron Emission Tomography/Computerised Tomography (PET/CT) to [123I]mIBG Imaging in Patients With Metastatic Neuroblastoma
This study aims to show that 3-dimensional PET/CT imaging with a new novel PET tracer (called [124I]mIBG) can detect as many or more sites of neuroblastoma (a type of childhood cancer) compared to the recommended 1-dimensional routine scans (called [123I]mIBG planar scintigraphy).
Read the detailed description
Neuroblastoma is the most common tumour of childhood after brain tumours. Approximately half of cases are high risk and despite extensive treatments outcome is very poor. More than 60% of high risk patients suffer relapse or further spread of their disease and long-term survival is below 10%. Existing imaging techniques are not sensitive enough to accurately assess the level of risk which is critical in determining the best choice of treatment. This study will compare a new type of imaging against the existing imaging techniques. The new scans use a new tracer called [124I]mIBG which is taken up by the cancer tissue much more than by normal tissues. This tracer can be used with a 3D imaging technique called PET/CT to pinpoint where the disease has spread and quantify the amount of disease. Patients will be those scheduled to have an [123I]mIBG scan for routine care during a planned break in treatment.
- Conditions
- Metastatic Neuroblastoma
- Being tested
- [124I]meta-Iodobenzylguanidine
- Keywords
- Neuroblastoma, Positron emission tomography, 124-iodine, Meta-Iodobenzylguanidine
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[124I]meta-IodobenzylguanidineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Trial | Experimental | This was a single arm trial, all patients were to undergo the same assessments and interventions. Receives: Drug: [124I]meta-Iodobenzylguanidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG Planar Scintigraphy Which Are Also Considered Positive With [124I]mIBG PET/CT.
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.
Measured: [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.
Secondary outcomes (2)
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
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.
Measured: [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.
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.
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.
Measured: Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completion15 Oct 2020
- Study completion15 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sue Chua, Dr, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02043899
- Sponsor's protocol ID
- CRUKD/12/002
- Other IDs
- 2012-002029-31
- Status last verified
- May 2021
- First submitted
- 21 Jan 2014
- Last updated
- 21 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cancer Research UK Phase I/II Study to Compare [124I]Meta-Iodobenzylguanidine (mIBG) Positron Emission Tomography/Computerised Tomography (PET/CT) to [123I]mIBG Imaging in Patients With Metastatic Neuroblastoma
- ClinicalTrials.gov ID
- NCT02043899
- Acronym / sponsor ID
- CRUKD/12/002
- Conditions
- Metastatic Neuroblastoma
- Keywords
- Neuroblastoma, Positron emission tomography, 124-iodine, Meta-Iodobenzylguanidine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Feb 2014 (actual)
- Primary completion
- 15 Oct 2020 (actual)
- Study completion
- 15 Oct 2020 (actual)
- First posted
- 23 Jan 2014 (estimated)
- Results
- Posted 21 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to show that 3-dimensional PET/CT imaging with a new novel PET tracer (called [124I]mIBG) can detect as many or more sites of neuroblastoma (a type of childhood cancer) compared to the recommended 1-dimensional routine scans (called [123I]mIBG planar scintigraphy).
Detailed description
Neuroblastoma is the most common tumour of childhood after brain tumours. Approximately half of cases are high risk and despite extensive treatments outcome is very poor. More than 60% of high risk patients suffer relapse or further spread of their disease and long-term survival is below 10%. Existing imaging techniques are not sensitive enough to accurately assess the level of risk which is critical in determining the best choice of treatment. This study will compare a new type of imaging against the existing imaging techniques. The new scans use a new tracer called [124I]mIBG which is taken up by the cancer tissue much more than by normal tissues. This tracer can be used with a 3D imaging technique called PET/CT to pinpoint where the disease has spread and quantify the amount of disease. Patients will be those scheduled to have an [123I]mIBG scan for routine care during a planned break in treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Trial | Experimental | Drug: [124I]meta-IodobenzylguanidineThis was a single arm trial, all patients were to undergo the same assessments and interventions. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically proven Stage 4 neuroblastoma as defined by the International Neuroblastoma Staging System (INSS).
- Aged ≥ 1 year at the time that written informed consent is given.
- Planned to undergo conventional [123I]mIBG planar scintigraphy for routine clinical care of neuroblastoma.
- Life expectancy of at least 12 weeks.
- World Health Organisation (WHO) performance status of 0, 1 or 2 for patients aged > 12 years old or Lansky play scale score of ≥ 50% for patients aged ≤ 12 years old.
Key exclusion criteria (16 listed)
- Treatment with any medications contra-indicated with mIBG scanning as listed in Appendix 4 of the trial protocol. For example, decongestants containing pseudoephedrine, phenylpropalomine and phenylephrine, sympathomimetics, cocaine, antihypertensives, tricyclic antidepressants. These drugs should be stopped before administration as indicated in this list (usually for four biological half-lives to allow almost complete wash-out but refer to list).
- Stage 4S neuroblastoma as defined by the INSS.
- Any anti-cancer treatment planned between the routine [123I]mIBG imaging and the [124I]mIBG PET/CT scan on Day 2. Anti-cancer treatments can be started only after the Off-Study assessment on Day 3 to Day 7, see schedule of assessments in Section 7. N.B. Patients should not be enrolled in the study if their participation will delay their subsequent treatment for neuroblastoma.
- Female patients who are pregnant or lactating.
- At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [124I]meta-IodobenzylguanidineSingle 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. | Drug | Single Arm Trial |
Primary outcome
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG Planar Scintigraphy Which Are Also Considered Positive With [124I]mIBG PET/CT.
Time frame: [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.
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.
2 secondary outcomes
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG SPECT Which Are Also Considered Positive With [124I]mIBG PET/CT.
Time frame: [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.
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.
Time frame: Safety data was collected from the date of written informed consent and continued for seven days after administration of [124I]mIBG.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sue Chua, Dr principal investigator
Royal Marsden NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing [124I]meta-Iodobenzylguanidine in people with Metastatic Neuroblastoma, run by Cancer Research UK at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the Number of Lesions Detected as Positive by [123I]mIBG Planar Scintigraphy Which Are Also Considered Positive With [124I]mIBG PET/CT. (time frame: [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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021.