68Ga-SATO in paediatric neuroblastoma patient; exploratory, safety, non-randomized, open label, comparative study - GAP NBL study*

Neuroblastoma is a relatively common malignancy in paediatric patients, with a
median age at diagnosis of 18.8 months. Approximately 80% of NBL patients has
MIBG positive disease. Unfortunately, both current clinical standards; imaging
with M123IBG and therapy with M131IBG have several disadvantages. As an
alternative, somatostatin receptor (SSTR) targeted imaging and therapy might
have several benefits over MIBG. Approximately 85% of recurrent or refractory
high risk neuroblastoma patients have positive SSTR2a staining at
histopathology. In low-, intermediate- and high (non-refractory) risk patients,
SSTR2a expression is even higher.1 In NBL tumours with MYNC-amplification, SSTR
expression is present, but to a lesser degree than in non-MYNC amplified NBL
tumors.1 Besides MYNC-amplification, in high risk NBL patients (INSS stage 3 or
4) SSTR expression was an independent predictor for overall survival,
potentially identifying a subgroup of high risk NBL patients with a poorer
survival.1 Experience exists with a SSTR subtype 2a agonist (i.e.
68Ga-DOTATOC). However, from a physiological perspective a SSTR antagonist
(i.e. 68Ga-Satoreotide trizoxetan, abbreviated to 68Ga-SATO), targeting both
activated as non-activated SSTR2a, seems better than a SSTR2a agonist.
With this observational pilot study, primarily we wish to assess the safety of
the new imaging radiopharmaceutical, SSTR-antagonist 68Ga-SATO and secondary,
compare its diagnostic accuracy to current clinical standard M123IBG and whole
body MRI (the latter in case of availability).

This study has been transitioned to CTIS with ID 2024-513843-10-00 check the CTIS register for the current data.

Primary objective:
Assess the short term safety and tolerability of 68Ga-SATO in pediatric
patients with NBL

Secondary objectives:
- Comparison of 68Ga-SATO PET/CT imaging to the current clinical standard of
M123IBG scintigraphy in NBL patients, in terms of lesions detection.
- Comparison of 68Ga-SATO PET/CT imaging to whole body MRI (in case available),
in terms of lesions detection.
- To calculate, in a subset of patients, the radiation absorbed dose of
68Ga-SATO for patients using dynamic PET imaging.
- Evaluation of procedure time for the preparations and acquisition of a
68Ga-SATO

exploratory see protocol section 1.0 objectives

A prospective explorative, investigator initiated, pilot study investigating
the accuracy and safety of 68Ga-SATO in NBL patients, compared to current
clinical standard, M123IBG imaging on 20 time points.

n.a.; an additional 68Ga-SATO PET/CT will be performed, for which the patient
will receive a single bolus injection of the radiopharmaceutical via a
pre-existing intravenous cannula or via a pre-existing central line.

An additional 68Ga-SATO PET/CT will be performed, for which the patient will
receive a single bolus injection of the radiopharmaceutical via a pre-existing
intravenous cannula or via a pre-existing central line.
Ideally, the PET/CT scan will be performed in the same anaesthesia session
(only in children requiring sedation), as the M123IBG scintigraphy, the
standard diagnostic investigation. This will increase the anaesthesia time by
30-40 minutes and will require no additional placement of an intravenous
cannula (for this study). Alternative logistically acceptable solutions are a)
the PET/CT will be acquired on the day of M123IBG injection (day prior to
M123IBG scintigraphy acquisition; not for children requiring anaesthesia) or on
the day of a MRI in standard of care (for patients requiring anaesthesia), b) a
separate acquisition day, not in combination with the standard diagnostic
M123IBG protocol, as long as the reference test (M123IBG scintigraphy) and the
68Ga-SATO PET/CT are not more than 2 weeks apart (only for children not
requiring anaesthesia).

Results of the 68Ga-SATO PET/CT will be blinded for the treating physician and
will not influence treatment decision making, as the clinical value of
68Ga-SATO of any other SSTR-targeted PET/CT is unknown to date. This study will
generate preliminary data for the initiation and development of future phase 2
studies in neuroblastoma.
No related adverse events are described in literature and are not expected
related to 68Ga-SATO. However, adverse events possibly, probably or
definitively related to the 68Ga-SATO will be monitored up to 1 hour after
PET/CT acquisition (=2 hours after administration). An additional telephone
visit will be planned 3-5 days after the scan to ask patients for new,
unexpected adverse events.

Potential harm for the child is the additional radiation exposure of the
radiopharmaceutical and additional low-dose CT. Based on data in adults, a
radiation exposure of 68Ga-SATO alone is approximately 3.6 mSv for a 150 MBq
injection. However, amount of activity for administration and image acquisition
will be adjusted to the patients weight in this study; 2 MBq/kg (minimum of 40
MBq, maximum 150 MBq). The additional low dose CT will be approximately 2 mSv
(in line with low dose CT acquisition in clinical 18FDG-PET/CT). For
comparison, in small children M123IBG alone results in a radiation exposure of
approx.. 3.2 mSv for the minimum dose of 80 MBq (according to SIOPEN
guidelines) and in adults 68Ga-DOTATOC results in radiation exposure of approx.
3.1 mSv for a 150 MBq injection (investigational brochure and EANM guideline).

Because of the one-day imaging schedule and the shorter acquisition time,
68Ga-SATO is more convenient for patients (and parents/caregivers). No
additional preparation is needed for image acquisition (no thyroid protection
from radioactive iodine, like with M123IBG or fasting for 4-12 hours, like with
18FDG).