Gastroenteropancreatic Neuroendocrine TumorsPhase 4NCT04524442
Post-Authorization Safety Study (PASS) of LysaKare® in Adult Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) Patients
A Phase 4 study testing arginine/lysine in people with Gastroenteropancreatic Neuroendocrine Tumors, run by Advanced Accelerator Applications at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastroenteropancreatic Neuroendocrine Tumors
- What is being tested?
- arginine/lysine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 25 Jan 2021to 18 Nov 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Pre-existing hyperkalemia (>6.0 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion. For Poland only, pre-existing hyperkalemia (> 5.5 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion.
- 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.
- Pre-existing hyperkalemia (> 5.5 mmol/L at screening) if not adequately corrected before starting the arginine/lysine solution infusion.
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United Kingdom4 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2GW
University Hospitals Coventry & Warwickshire NHS Trust
Coventry, CV2 2DX
Royal Surrey Country Hospital
Guildford, GU2 7XX
Liverpool Royal Hospital
Liverpool, L7 8YA
Netherlands1 site
Erasmus University Medical Center
Rotterdam, Gelderland, 3015
About this 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
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.
Read the 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.
- Being tested
- arginine/lysine
- Keywords
- 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
- Medical subject headings
- Gastro-enteropancreatic neuroendocrine tumor, Neuroendocrine Tumors, Carcinoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arginine/lysineDrug
Also called LysaKare
1000 milliliters (mL) administered at a constant rate of 250 mL per hour
| Study group | Role | What they receive |
|---|---|---|
| GEP-NET | Experimental | One dose of arginine/lysine solution administered intravenously over a 4-hour period Receives: Drug: arginine/lysine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0/Infusion Day (Hour 0, Hour 2, Hour 4, Hour 6, Hour 8, Hour 12, Hour 24)
Secondary outcomes (9)
Percentage of Participants With Treatment Adverse Events (AEs) & Serious Adverse Events (SAEs)
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).
Measured: 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: (systolic blood pressure, diastolic blood pressure, pulse rate \& weight) compared to baseline.
Measured: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Number of Participants With Notable Changes in Electrocardiogram (ECG)
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
Measured: 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 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.
Measured: 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. 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.
Measured: Day 0/Infusion Day (0 and 24 hours)
Number of Participants With Notable Changes in Electrolyte Parameters
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.
Measured: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, pH, Over 24 Hours
Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: pH.
Measured: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, Lactic Acid, Over 24 Hours
Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Lactic Acid
Measured: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, Partial Pressure Carbon Dioxide, Over 24 Hours
Safety measured by the mean changes in blood gas compared to baseline. Blood gas parameter: Partial Pressure Carbon Dioxide.
Measured: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start25 Jan 2021
- Primary completion18 Nov 2023
- Study completion18 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gastroenteropancreatic Neuroendocrine TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advanced Accelerator Applications
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04524442
- Sponsor's protocol ID
- CAAA001A12401
- Other IDs
- 2019-004073-76, 2019
- Status last verified
- Jan 2025
- First submitted
- 20 Aug 2020
- Last updated
- 24 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04524442
- Acronym / sponsor ID
- CAAA001A12401
- Keywords
- GEP-NET, Neuroendocrine tumors, NETs, carcinoid tumors, LysaKare, arginine/lysine, amino acid, Peptide Receptor Radionuclide Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Advanced Accelerator ApplicationsIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2021 (actual)
- Primary completion
- 18 Nov 2023 (actual)
- Study completion
- 18 Nov 2023 (actual)
- First posted
- 24 Aug 2020 (actual)
- Results
- Posted 24 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GEP-NET | Experimental | Drug: arginine/lysineOne dose of arginine/lysine solution administered intravenously over a 4-hour period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- Pre-existing hyperkalemia (>6.0 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion. For Poland only, pre-existing hyperkalemia (> 5.5 mmol/L at screening) if not adequately corrected before starting the LysaKare (arginine/lysine) infusion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| arginine/lysineAlso: LysaKare1000 milliliters (mL) administered at a constant rate of 250 mL per hour | Drug | GEP-NET |
Primary outcome
Mean Change From Baseline in Serum Potassium Levels Over 24 Hours
Time frame: 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.
9 secondary outcomes
Percentage of Participants With Treatment Adverse Events (AEs) & Serious Adverse Events (SAEs)
Time frame: Day 0/Infusion Day up to 48 hours post infusion
Number of Participants With Notable Changes in Vital Signs
Time frame: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Number of Participants With Notable Changes in Electrocardiogram (ECG)
Time frame: Day 0/Infusion Day (0, 4, 8 and 24 hours)
Number of Participants With Notable Changes in Hematology Parameters
Time frame: Day 0/Infusion Day (0 and 24 hours)
Number of Participants With Notable Changes in Chemistry Parameters
Time frame: Day 0/Infusion Day (0 and 24 hours)
Number of Participants With Notable Changes in Electrolyte Parameters
Time frame: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, pH, Over 24 Hours
Time frame: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, Lactic Acid, Over 24 Hours
Time frame: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Mean Change From Baseline in Blood Gas Parameter, Partial Pressure Carbon Dioxide, Over 24 Hours
Time frame: Day 0/Infusion Day (0, 2, 4, 6, 8, 12 and 24 hours)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing arginine/lysine in people with Gastroenteropancreatic Neuroendocrine Tumors, run by Advanced Accelerator Applications at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United Kingdom, Italy, Netherlands, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Serum Potassium Levels Over 24 Hours (time frame: Day 0/Infusion Day (Hour 0, Hour 2, Hour 4, Hour 6, Hour 8, Hour 12, Hour 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2025.