Trial Outcomes & Findings for Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs (NCT NCT04711135)

Last Updated: 2025-07-17

Results Overview

Absorbed radiation doses in target organ (e.g. kidney and bone marrow) was evaluated when all Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) and Pheochromocytoma and paraganglioma (PPGLs) as a pooled cohort patients had completed the 1st treatment of Lutathera and completed the dosimetry assessment.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Up to 8 days after the first Lutetium [Lu 177] dotatate dose

Results posted on

2025-07-17

Participant Flow

At the data cut-off (DCO) date (12-Mar-2024) for this primary analysis 11 participants were enrolled across 7 centers.

The study schedule for each participant consisted of the screening period (up to 2 weeks) followed by the treatment period and the follow-up period.

Participant milestones

Participant milestones
Measure	GEP-NET All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Overall Study STARTED	4	7
Overall Study Ongoing Treatment	0	1
Overall Study Entered Short Term Follow-up	4	5
Overall Study Entered Long Term Follow-up	1	3
Overall Study COMPLETED	4	5
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	GEP-NET All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Overall Study Physician Decision	0	1
Overall Study Ongoing treatment	0	1

Baseline Characteristics

Study to Evaluate Safety and Dosimetry of Lutathera in Adolescent Patients With GEP-NETs and PPGLs

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GEP-NET n=4 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL n=7 Participants All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	Total n=11 Participants Total of all reporting groups
Age, Continuous	15.5 years STANDARD_DEVIATION 0.58 • n=5 Participants	14.9 years STANDARD_DEVIATION 1.77 • n=7 Participants	15.1 years STANDARD_DEVIATION 1.45 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 8 days after the first Lutetium [Lu 177] dotatate dose

Population: Dosimetry Analysis Set (DAS): The DAS consisted of all participants who had at least one valid (i.e., not flagged for exclusion by the dosimetrist) dosimetry measurement.

Outcome measures

Outcome measures
Measure	GEP-NET n=4 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL n=6 Participants All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Absorbed Radiation Doses in Target Organ Kidney	0.71 Gy/GBq Standard Deviation 0.25	0.82 Gy/GBq Standard Deviation 0.32
Absorbed Radiation Doses in Target Organ Pituitary	1.2 Gy/GBq Standard Deviation 0.43	1.0 Gy/GBq Standard Deviation 0.45
Absorbed Radiation Doses in Target Organ Red Marrow (Blood)	0.024 Gy/GBq Standard Deviation 0.0035	0.028 Gy/GBq Standard Deviation 0.0052
Absorbed Radiation Doses in Target Organ Red Marrow (Image)	0.043 Gy/GBq Standard Deviation 0.018	0.067 Gy/GBq Standard Deviation 0.028
Absorbed Radiation Doses in Target Organ Spleen	0.63 Gy/GBq Standard Deviation 0.39	0.82 Gy/GBq Standard Deviation 0.17
Absorbed Radiation Doses in Target Organ Urinary Bladder Wall	0.50 Gy/GBq Standard Deviation 0.034	0.59 Gy/GBq Standard Deviation 0.096
Absorbed Radiation Doses in Target Organ Total Body	0.040 Gy/GBq Standard Deviation 0.013	0.041 Gy/GBq Standard Deviation 0.0073

PRIMARY outcome

Timeframe: during first cycle of Lutetium [Lu 177] dotatate treatment (Cycle = 56 days)

Population: Safety Set: The Safety Set included all participants that received at least one dose of Lutathera.

Safety in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort was evaluated through the incidence of AEs and laboratory abnormalities after the first Lutathera dose.

Outcome measures

Outcome measures
Measure	GEP-NET n=4 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL n=7 Participants All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Incidence of Adverse Events (AEs) and Lab Toxicities After 1st Lutathera Administration	4 Participants	6 Participants

SECONDARY outcome

Timeframe: From first Lutetium [Lu 177] dotatate dose to 6 months after last dose, approx. 12 months

Population: Safety Set: The Safety Set included all participants that received at least one dose of Lutathera.

Cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort was assessed through the incidence of adverse events (AEs) and laboratory toxicities until 6 months after the last Lutathera dose.

Outcome measures

Outcome measures
Measure	GEP-NET n=4 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL n=7 Participants All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Incidence of Adverse Events (AEs) During Treatment and Short-term Follow-up AEs during Lutathera treatment	4 Participants	7 Participants
Incidence of Adverse Events (AEs) During Treatment and Short-term Follow-up AEs during short-term follow-up	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 5 years after the last Lutetium [Lu 177] dotatate dose

Long-term safety of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort was evaluated through the incidence of AEs and laboratory abnormalities during the 5-year follow-up after the last Lutathera dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After 4 cycles of 7.4 GBq/200 mCi; each cycle is 8+/-1 weeks

Population: Dosimetry Analysis Set (DAS) consisted of all participants who had at least one valid dosimetry measurement. Original NETTER-P protocol intended to conduct separate analyses for the GEP-NET and the PPGL populations. However, the protocol was amended to allow combined analyses for dosimetry across the two patient indications. The number of patients was equal 10, since data from one patient was excluded from the dosimetry modeling analysis, due to technical issues during image acquisitions.

A comparative assessment of dosimetry for organs at risk specifically kidneys and bone marrow, was performed between adolescent patients with GEP-NETs and PPGLs as a pooled cohort and adult patients using the extrapolation model developed for the clinical study to confirm the probability of exceeding 29 Gy (kidneys) \& 2 Gy (bone marrow) thresholds.

Outcome measures

Outcome measures
Measure	GEP-NET n=10 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Calculated Probability of Exceeding the Kidney and Bone Marrow External Beam Radiation Therapy (EBRT) Threshold Observed: Kidney (Probability (%) >29 Gy)	20.0 probability	—
Calculated Probability of Exceeding the Kidney and Bone Marrow External Beam Radiation Therapy (EBRT) Threshold Observed: Bone Marrow (Probability (%) >2 Gy)	0.0 probability	—

SECONDARY outcome

Timeframe: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose

Population: The PK Analysis Set (PKAS) consisted of all participants who had at least one valid (i.e., not flagged for exclusion) PK measurement. Original NETTER-P protocol intended to conduct separate analyses for the GEP-NET and the PPGL populations. However, the protocol was amended to allow combined analyses for PK across the two patient indications.

A comparative assessment of PK will be performed between Observed and Predicted adolescent patients with GEP-NETs and PPGLs as a pooled cohort and adult patients using the extrapolation model developed for the clinical study. The observed PK metrics were calculated using non-compartmental analysis (NCA), the predicted PK metrics were derived based on the adolescent population pharmacokinetics (popPK) model.

Outcome measures

Outcome measures
Measure	GEP-NET n=11 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Pharmacokinetics (PK) Parameter: AUClast - Based on Blood Radioactivity Concentration Data Observed	41 ng.h/mL Geometric Coefficient of Variation 24.15	—
Pharmacokinetics (PK) Parameter: AUClast - Based on Blood Radioactivity Concentration Data Predicted	32.34 ng.h/mL Geometric Coefficient of Variation 10.43	—

SECONDARY outcome

Timeframe: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose

Outcome measures

Outcome measures
Measure	GEP-NET n=11 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Pharmacokinetics (PK) Parameter: Cmax - Based on Blood Radioactivity Concentration Data Observed	11.17 ng/mL Geometric Coefficient of Variation 33.04	—
Pharmacokinetics (PK) Parameter: Cmax - Based on Blood Radioactivity Concentration Data Predicted	10.31 ng/mL Geometric Coefficient of Variation 5.22	—

SECONDARY outcome

Timeframe: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose

Outcome measures

Outcome measures
Measure	GEP-NET n=11 Participants All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.
Pharmacokinetics (PK) Parameter: Tmax - Based on Blood Radioactivity Concentration Data Observed	0.58 hr Interval 0.5 to 0.77	—
Pharmacokinetics (PK) Parameter: Tmax - Based on Blood Radioactivity Concentration Data Predicted	0.5 hr Interval 0.5 to 0.7	—

Adverse Events

GEP-NET

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

PPGL

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Total

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GEP-NET n=4 participants at risk All eligible participants with Gastroenteropancreatic neuroendocrine tumor (GEP-NET) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	PPGL n=7 participants at risk All eligible participants with Pheochromocytoma and paraganglioma (PPGL) received at least one dose of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8+/-1 weeks; cumulative dose: 29.6 GBq/800 mCi), with a concomitant administration of 2.5% Lysine - Arginine amino acid solution.	Total n=11 participants at risk All participants from the GEP-NET and PPGL arms.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	25.0% 1/4 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/7 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	9.1% 1/11 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.
Infections and infestations Device related infection	0.00% 0/4 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	14.3% 1/7 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	9.1% 1/11 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.
Metabolism and nutrition disorders Hypercalcaemia	25.0% 1/4 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	0.00% 0/7 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.	9.1% 1/11 • AEs & on-treatment deaths were collected from the first dose of study treatment up to data cut-off date of 12-Mar-2024, approx. 19 months from the FPFV. Any sign or symptom that occurs during the conduct of the trial.

Other adverse events

Additional Information

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