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

Phase 4

Completed

Conditions: Gastroenteropancreatic Neuroendocrine Tumors

Interventions: Drug: arginine/lysine

Registration Number: NCT04524442

Lead Sponsor: Advanced Accelerator Applications

Brief Summary: The purpose of the study was to evaluate the effect of arginine/lysine solution administration on serum potassium levels. A systematic assessment of serum potassium levels was performed during infusion and up to 24 hours post start of infusion compared to baseline.

Detailed Description: The study schedule for each patient consisted 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 was determined according to inclusion and exclusion criteria, with evaluation of patient's vital signs, ECG and laboratory parameters. The duration of screening could be as short as one day but could not exceed 7 days. Patients who showed potassium level \> 6.0 mmol/L (\> 5.5 mmol/L for Poland only) at screening could have their potassium level corrected and could be re-screened afterwards.

Treatment Phase:

Eligible patients were admitted to the in-clinic unit and dosed with arginine/lysine solution for infusion of 1,000 mL, which was administered intravenously over a period of 4 hours. Before the infusion (at 0 h time point), a set of baseline tests were performed. During and after the infusion, patient condition was monitored for evaluation of any adverse events. Only patients with a potassium level of ≤ 6 mmol/L at screening (\> 5.5 mmol/L for Poland only) were allowed to be dosed. Potassium testing on the infusion day was performed at 0h (before the infusion), and at 2h, 4h, 6h, 8h, 12h, and 24h after the start of infusion. Vital signs and ECGs were taken as specified in the assessment schedule. All patients were 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 was given. The choice of anti-emetic drugs was at the discretion of the physician.

Follow-up Phase:

All patients were called for a safety follow-up in 48 hours after dosing. Patients were not 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GEP-NET	arginine/lysine	One dose of arginine/lysine solution administered intravenously over a 4-hour period

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Serum Potassium Levels Over 24 Hours	Day 0/Infusion Day (Hour 0, Hour 2, Hour 4, Hour 6, Hour 8, Hour 12, Hour 24)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Adverse Events (AEs) & Serious Adverse Events (SAEs)	Day 0/Infusion Day up to 48 hours post infusion	Safety measured by the percentage of participants with treatment emergent adverse events (starting from the signing of the ICF until the end of the follow-up call (48 hours after infusion).
Number of Participants With Notable Changes in Vital Signs	Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)	Safety measured by the notable post-baseline changes in vital signs: (systolic blood pressure, diastolic blood pressure, pulse rate \& weight) compared to baseline.
Number of Participants With Notable Changes in Electrocardiogram (ECG)	Day 0/Infusion Day (0, 4, 8 and 24 hours)	Safety measured by the notable post-baseline changes in ECG values compared to baseline PR, QRS, QT, QTcF, and RR intervals were obtained from 12-lead ECGs for each subject during the study
Number of Participants With Notable Changes in Hematology Parameters	Day 0/Infusion Day (0 and 24 hours)	Safety measured by the notable post-baseline changes in Hematology parameters compared to baseline as represented by Shift tables based on common toxicity criteria (CTC) grades. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline.
Number of Participants With Notable Changes in Chemistry Parameters	Day 0/Infusion Day (0 and 24 hours)	Safety measured by the notable post-baseline changes in Chemistry parameters compared to baseline. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline. Key shifts were in the following parameters: creatinine, lactate dehydrogenase and creatinine clearance.
Number of Participants With Notable Changes in Electrolyte Parameters	Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)	Safety measured by the notable post-baseline changes in Electrolyte parameters compared to baseline. Each participant was counted only for the worst grade observed post-baseline. Notable change is the shift to higher grades from baseline.
Mean Change From Baseline in Blood Gas Parameter, pH, Over 24 Hours	Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)	Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: pH.
Mean Change From Baseline in Blood Gas Parameter, Lactic Acid, Over 24 Hours	Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)	Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Lactic Acid
Mean Change From Baseline in Blood Gas Parameter, Partial Pressure Carbon Dioxide, Over 24 Hours	Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)	Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Partial Pressure Carbon Dioxide.

Trial Locations

Locations (7): Istituto Europeo di Oncologia
🇮🇹
Milan, MI, Italy
Erasmus University Medical Center
🇳🇱
Rotterdam, GD, Netherlands
Gammed-Centrum Diagnostyczno-Lecznicze
🇵🇱
Warsaw, Poland
University Hospitals Birmingham NHS Foundation Trust
🇬🇧
Birmingham, United Kingdom
University Hospitals Coventry & Warwickshire NHS Trust
🇬🇧
Coventry, United Kingdom
Royal Surrey Country Hospital
🇬🇧
Guildford, United Kingdom
Liverpool Royal Hospital
🇬🇧
Liverpool, United Kingdom