A multicenter open-label study to evaluate safety and dosimetry of Lutathera in adolescent patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine (GEP-NET) tumors, pheochromocytoma and paragangliomas

There are currently no approved therapies for GEP-NETs in the pediatric
population. As observed in adults, the diagnosis of NETs in children is often
delayed due to the indolent nature of the disease. It has been reported that
10% to 20% of pediatric patients present with metastatic disease at diagnosis.
While surgical intervention is favored as first-line treatment for patients
with early-stage disease, metastatic GEP-NETs in the pediatric population, as
in adults, are often unresectable. Non-surgical treatment modalities for the
pediatric population include those used in adults, namely, somatostatin
analogues, chemotherapy, everolimus, and peptide receptor radionuclide therapy
(PRRTs). A small number of published studies have reported data on the use of
Lutathera in children and adolescents with neuroblastomas, or with 90Y-DOTATOC
in pediatric GEP-NETs. There are no published studies on the use of Lutathera
in pediatric GEP-NETs.
Given the limitations of approved therapeutic options for the GEP-NET and PPGL
pediatric population, these diseases in adolescents constitute an area of high
unmet need. This clinical study aims to address this unmet need and to
accelerate access of Lutathera as a potential treatment for adolescent patients
with a primary focus on GEP-NETs. Due to the rarity of pediatric data in PPGL
and unmet need in this indication, an exploratory cohort will be open for
enrolment of adolescent patients with somatostatin receptor positive PPGLs.

Primary objectives:
• Evaluate organ absorbed radiation doses from PRRT with Lutathera in
adolescent patients with SSTR-positive GEP-NETs
• Evaluate safety and tolerability of Lutathera in adolescents with
SSTR-positive GEP-NETs

Secondary objectives:
• Evaluate cumulative safety of Lutathera in adolescents with SSTR-positive
GEP-NETs
• Evaluate long-term safety of Lutathera in adolescents with SSTR-positive
GEP-NETs
• Perform comparative assessment of dosimetry and pharmacokinetics (PK) between
adolescent patients with GEP-NET and adult patients using the extrapolation
model developed for the clinical study

This is a multicenter, open-label, single-arm study to evaluate the safety and
dosimetry of Lutathera in adolescent patients 12 to <18 years old with
somatostatin receptor positive GEP-NETs and PPGLs. The study will enroll at
least 8 patients in the GEP-NET cohort and as many adolescents with PPGL as
possible in the exploratory PPGL cohort.The study schedule for each patient
consists of the screening period (up to 2 weeks) followed by the treatment
period (4 treatment administrations at 8-week intervals), and the follow-up
period (5 years).

Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks; cumulative dose:
29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine
amino acid (AA) solution

Participation in the study will consist of about 6 months of treatment and 5
years of follow-up. During that time, participants will need to visit the study
site about 32 times. Out of these 32 visits, some visits can be done remotely,
through a phone call with the investigator. Most study visits should take about
2-3 hours. However, the visits to the study site when Lutathera is
administered, as well as the visits during 1st week when radioactivity is
measured, will be longer. Aside from the intervention described above,
participation in this study involves blood draws at multiple visits, radiation
exposure through CT, SRI, SPECT/CT and whole body planar imaging. Participants
will be subjected to: questions regarding medical history, use of concomitant
medications/procedures and adverse events; MRI scans; urine sampling;
measurement of vital signs; physical examination; ECGs, and patient reported
outcomes questionnaires.

Very common side effects related to the study drug (happens to about 1 in 10
people) include low platelet count, low white blood cell count, low red cell
count, decreased all blood cell count (pancytopenia), decreased appetite,
nausea, vomiting and fatigue.
The most common side effects of amino acid administration are nausea
(approximately 25%) and vomiting (approximately 10%).
Possible risks related to the IV infusion are: infection, inflammation of the
vein, infiltration, extravasation (where the drug leaks into the surrounding
tissues outside of the vein) and embolism (obstruction in a blood vessel).
In addition, there is a risk due to increased radiation exposure from the CT,
SRI, SPECT/CT and whole body planar imaging.

Considering the age of participants, additional potential safety concerns in
the pediatric population will be controlled via assessment of safety
biomarkers. This includes potential effects of treatment with Lutathera on
endocrine (hypothalamic-pituitary) function, gonadal function, growth and bone
development that will be controlled during and after the treatment with
Lutathera.
All safety effects of Lutathera will be carefully assessed in this study, and
patients will be closely monitored.
As this is the first study of Lutathera in adolescents with GEP-NETs and PPGLs,
its efficacy and safety has not been established in this population yet.
However, based on adult efficacy and similarities between adolescents and
adults, it is expected that Lutathera administered in the study may bring
therapeutic benefit to adolescents with GEP-NETs and PPGLs. This study will be
essential to bring new potential therapeutic options for adolescent GEP-NET and
PPGL patients.