A Phase I/II Study of [124I]mIBG PET/CT in 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).

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.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically proven Stage 4 neuroblastoma as defined by the International Neuroblastoma Staging System (INSS).
2. Aged ≥ 1 year at the time that written informed consent is given.
3. Planned to undergo conventional \[123I\]mIBG planar scintigraphy for routine clinical care of neuroblastoma.
4. Life expectancy of at least 12 weeks.
5. 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.
6. 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).

Exclusion Criteria:

1. 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).
2. Stage 4S neuroblastoma as defined by the INSS.
3. 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.
4. Female patients who are pregnant or lactating.
5. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
6. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
7. Patients with known hypersensitivity to mIBG.
8. 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

1. 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.
2. ≥ 3kg at the time of the \[124I\]mIBG imaging to agree with the paediatric EANM guidelines.
3. 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.
4. 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.
5. 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.