Post-Authorization Safety Study (PASS) of LysaKare® in Adult Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the effect of arginine/lysine solution administration on serum potassium levels. A systematic assessment of serum potassium levels will be performed during infusion and up to 24 hours post start of infusion compared to baseline.

Detailed Description
-----------------
The study schedule for each patient consists of a screening period followed by an infusion day with an optional overnight in-clinic stay, and a follow up call 48h post infusion. Screening Phase: At screening, patient eligibility will be determined according to inclusion and exclusion criteria, with evaluation of patient's vital signs, ECG and laboratory parameters. The duration of screening can be as short as one day but should not exceed 7 days. Patients who show potassium level > 6 mmol/L at screening should have their potassium level corrected and can be re-screened afterwards. Treatment Phase: Eligible patients will be admitted to the in-clinic unit to be dosed with arginine/lysine solution for infusion of 1,000 mL, which is administered intravenously over a period of 4 hours. Before the infusion (at 0 h time point), a set of baseline tests will be performed. During and after the infusion, patient condition will be monitored for evaluation of any adverse events. Only patients with a potassium level of ≤ 6 mmol/L at screening will be allowed to be dosed. Potassium testing on the infusion day will be performed at 0h (before the infusion), and at 2h, 4h, 6h, 8h, 12h, and 24h after the start of infusion. Vital signs and ECGs will be taken as specified in the assessment schedule. All patients will be monitored closely for signs and symptoms of hyperkalemia, e.g. dyspnoea, weakness, numbness, chest pain and cardiac manifestations (conduction abnormalities and cardiac arrhythmias). Other common adverse reactions during arginine/lysine solution administration are nausea and vomiting. Before the start of arginine/lysine solution infusion, an intravenous bolus of an anti-emetic should be given. The choice of anti-emetic drugs is at the discretion of the physician. Follow-up Phase: All patients will be called for a safety follow-up in 48 hours after dosing. Patients should not be scheduled to receive repeat dosing with arginine/lysine solution as concomitant medication with Lutathera® within 7 days of the arginine/lysine solution infusion in the study.

Official Title
-----------------
A Multicenter, Open-label Post Authorization Safety Study to Evaluate the Effect of LysaKare® Infusion on Serum Potassium Levels in GEP-NET Patients Eligible for Lutathera® Treatment

Conditions
-----------------
Gastroenteropancreatic Neuroendocrine Tumors

Intervention / Treatment
-----------------
* Drug: arginine/lysine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), who are eligible for the treatment with Lutathera as per Lutathera label indication. Patients who have provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related procedures. Exclusion Criteria: Pre-existing hyperkalemia (>6.0 mmol/L at screening) if not adequately corrected before starting the arginine/lysine solution infusion (applicable to all countries except Poland). Instances when Lutathera is not recommended per the Lutathera Summary of Product Characteristics (SmPC). Pregnancy or lactation, positive pregnancy test at screening or pre-dose based on the contraindication for Lutathera. Any significant medical or social condition which may interfere with the subject's ability to comply with the study visit schedule or the study assessments. Patients who have received any investigational agent within the last 30 days. Patients that have received a dose of Lutathera prior to the screening visit or are scheduled for Peptide Receptor Repeat (PRRT) treatment within 7 days of the study infusion of arginine/lysine solution. Other protocol-defined exclusion criteria may apply. Exclusion Criteria (Poland Only): - Pre-existing hyperkalemia (> 5.5 mmol/L at screening) if not adequately corrected before starting the arginine/lysine solution infusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEP-NET<br>One dose of arginine/lysine solution administered intravenously over a 4-hour period | Drug: arginine/lysine<br>* 1000 milliliters (mL) administered at a constant rate of 250 mL per hour<br>* Other names: LysaKare;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in serum potassium levels over 24 hours | Serum potassium levels at each collection time point will be measured at local laboratories of study sites using validated methods. The potassium concentration results will be summarized descriptively and will include mean change, maximum change, time to the maximum change, and the overall dynamics of the potassium concentration curve during and after the arginine/lysine infusion. | Day 0/Infusion Day (Hour 0, Hour 2, Hour 4, Hour 6, Hour 8, Hour 12, Hour 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with treatment emergent adverse events | Safety measured by the percentage of participants with treatment emergent adverse events (events started after the first dose of study medication or events present prior to start of treatment but increased in severity based on preferred term). | Day 0/Infusion Day up to 48 hours post infusion | 
| Number of Participants with Notable Changes in vital signs | Safety measured by the notable post-baseline changes in vital signs compared to baseline. | Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours) | 
| Number of Participants with Notable Changes in ECG | Safety measured by the notable post-baseline changes in ECG values compared to baseline | Day 0/Infusion Day (0, 4, 8 and 24 hours) | 
| Number of Participants with Notable Changes in Hematology parameters | Safety measured by the notable post-baseline changes in Hematology parameters compared to baseline | Day 0/Infusion Day (0 and 24 hours) | 
| Number of Participants with Notable Changes in Chemistry parameters | Safety measured by the notable post-baseline changes in Chemistry parameters compared to baseline | Day 0/Infusion Day (0 and 24 hours) | 
| Number of Participants with Notable Changes in Electrolyte and Blood Gas parameters | Safety measured by the notable post-baseline changes in Electrolyte and Blood Gas parameters compared to baseline | Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GEP-NET, Neuroendocrine tumors, NETs, carcinoid tumors, LysaKare, arginine/lysine, amino acid, Peptide Receptor Radionuclide Therapy, PRRT, Lutathera, Lutetium Lu 177 oxodotreotide, Lutetium Lu 177 dotatate