AzTrials
AzTrials

Gastroenteropancreatic Neuroendocrine TumorsPhase 2NETTER-PNCT04711135

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

A Phase 2 study testing Lutetium [177Lu] oxodotreotide/dotatate in people with Gastroenteropancreatic Neuroendocrine Tumors and Pheochromocytoma, run by Advanced Accelerator Applications at 7 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 12 to 17 years
What is being tested?
Lutetium [177Lu] oxodotreotide/dotatate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
7 sitesin 5 countries
Study dates
31 Aug 2022to 6 Feb 2034
Phase
Phase 2
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 12 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • GEP-NET cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven, G1 or G2 (Ki-67 index =< 20%), well differentiated GEP-NET.
  • or PPGL cohort: presence of metastasized or locally advanced, inoperable (curative intent), histologically proven PPGL.
  • Patients from 12 to < 18 years of age at the time of enrollment.
  • Expression of somatostatin receptors confirmed by a somatostatin receptor imaging (SRI) modality within 3 months prior to enrollment, with tumor uptake observed in the target lesions more or equal to the normal liver uptake.
  • Performance status as determined by Karnofsky score >= 50 or Lansky Play-Performance Scale score >= 50.
  • Parent's ability to understand and the willingness to sign a written informed consent document for adolescents as determined by local regulations. Adolescents will sign assent along with parental/legal guardian consent or will co-sign consent with parent/legal guardian in accordance with local regulation, prior to participation in the study.

Who cannot join

  • Laboratory parameters:
  • Estimated creatinine clearance calculated by the Cockroft-Gault method < 70 mL/min
  • Hb concentration <5.0 mmol/L (<8.0 g/dL); WBC <2x109/L; platelets <75x109/L.
  • Total bilirubin >3 x ULN for age.
  • Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
  • Established or suspected pregnancy.
Show all 16Show fewer
  • Breastfeeding female patients unless they accept to discontinue breastfeeding from the 1st dose until 3 months after the last administration of study drug.
  • Female patients of child-bearing potential, unless they are using highly effective methods of contraception during treatment and for 6 months after the last dose of Lutathera.
  • Sexually active male patients, unless they agree to remain abstinent or be willing to use effective methods of contraception.
  • Patients for whom in the opinion of the investigator other therapeutic options are considered more appropriate than the therapy offered in the study, based on patient and disease characteristics.
  • Current spontaneous urinary incontinence.
  • Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years.
  • Hypersensitivity to the study drug active substance or to any of the excipients.
  • Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
  • Patient with known incompatibility to CT Scans with I.V. contrast due to allergic reaction or renal insufficiency. If such a patient can be imaged with MRI, then the patient would not be excluded.
  • Patients who received any investigational agent within the last 30 days.

Trial locations and contacts

7 sites in 5 countries.

7 sites in 5 countries

United States3 sites
  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229-3039

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

France1 site
  • Centre Léon Berard

    Lyon

Other trials in France

Poland1 site
  • Maria Sklodowska-Curie National Research Institute of Oncology

    Gliwice

Other trials in Poland

Spain1 site
  • Hospital Universitari Vall d'Hebron

    Barcelona

Other trials in Spain

United Kingdom1 site
  • University College Hospital of London

    London

Other trials in United Kingdom

About this study

Official title: 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 (PPGL)

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.

Read the detailed description

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 interval), and the follow-up period (10 years).

The treatment period will consist of 4 Lutathera treatments administered at 8-week intervals. Lutathera administration will occur on Week 1 Day 1 of each cycle. Each patient will receive a total of 4 doses of Lutathera (7.4 GBq/200 mCi x 4 administrations every 8 weeks; cumulative dose: 29.6 GBq/800 mCi). An infusion of 2.5% Lysine - Arginine amino acid (AA) solution will be co-administered with each Lutathera dose for renal protection according to the approved Lutathera local prescribing information. An antiemetic will be administered prior to infusion of the AA solution for prevention of infusion-related nausea and vomiting.

The dosimetry and PK assessments will be performed during the first week after the 1st Lutathera dose, i.e. one time during the study treatment period for each patient. The dosimetry analysis will allow for estimation from the 1st Lutathera administration of the cumulative absorbed radiation dose from 4 Lutathera doses and also for taking a decision on the next dose levels. In the exceptional circumstances when dosimetry cannot be performed in a particular patient after the first Lutathera dose, it should be completed as soon as feasible upon a later dose. In order to minimize risk for each study subject, an accelerated analysis of dosimetry and safety data will be performed for each patient in the study, to enable the Investigator to take a decision for the subsequent Lutathera doses. The results of dosimetry assessments (imaging and blood dosimetry) will be provided to the investigators for their evaluation prior to administration of subsequent therapeutic cycles in each patient.

A total follow-up period of 10 years (120 months) after the last Lutathera dose will take place for each patient who received at least one dose of Lutathera. This follow-up period will be comprised of a short-term follow-up of 6 months to evaluate cumulative Lutathera toxicities, followed by a long-term follow up of another 114 months.

An external Data and Safety Monitoring Board (DSMB) will also operate in the study to evaluate accumulating safety and dosimetry data, to ensure the safety of adolescents enrolled in the study, and to provide recommendations to investigators as well as to the clinical team in charge of conducting the study.

Being tested
Lutetium [177Lu] oxodotreotide/dotatate
Keywords
GEP-NET, PPGL, adolescents, pediatric, Lutathera, Lutetium [177Lu] oxodotreotide, Lutetium Lu 177 dotatate, Peptide Receptor Radionuclide Therapy, PRRT
Medical subject headings
Pheochromocytoma, Paraganglioma, Gastro-enteropancreatic neuroendocrine tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lutetium [177Lu] oxodotreotide/dotatateDrug

    Also called Lutathera

    Radiopharmaceutical solution for infusion (7.4 GBq of Lutathera per 30 ml vial)

Study groups in NCT04711135
Study groupRoleWhat they receive
GEP-NET and PPGLExperimentalAll eligible participants will receive 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 solution.
Receives: Drug: Lutetium [177Lu] oxodotreotide/dotatate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absorbed Radiation Doses in Target Organ

    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.

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

  2. Incidence of Adverse Events (AEs) and Lab Toxicities After 1st Lutathera Administration

    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.

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

Secondary outcomes (6)
  1. Incidence of Adverse Events (AEs) During Treatment and Short-term Follow-up

    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.

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

  2. Incidence of Adverse Events (AEs) During the Long Term Follow-up

    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.

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

  3. Calculated Probability of Exceeding the Kidney and Bone Marrow External Beam Radiation Therapy (EBRT) Threshold

    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.

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

  4. Pharmacokinetics (PK) Parameter: AUClast - Based on Blood Radioactivity Concentration Data

    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.

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

  5. Pharmacokinetics (PK) Parameter: Cmax - Based on Blood Radioactivity Concentration Data

    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.

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

  6. Pharmacokinetics (PK) Parameter: Tmax - Based on Blood Radioactivity Concentration Data

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2021
  2. Study start31 Aug 2022
  3. Primary completion12 Mar 2024
  4. Study completion6 Feb 2034 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04711135
Sponsor's protocol ID
CAAA601A32201
Other IDs
2020-002951-39, EMEA-002950-PIP01-20, 2023-507444-37-00, 2023
Acronym
NETTER-P
Status last verified
Jan 2026
First submitted
16 Dec 2020
Last updated
12 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
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

Publications

  • Gaze MN, Handkiewicz-Junak D, Hladun R, Laetsch TW, Sorge C, Sparks R, Wan S, Ceraulo A, Kluczewska-Galka A, Gamez-Cenzano C, States LJ, El Khouli R, Aimone P, Perraud K, Kollar G, Khanshan F, Blumenstein L, Brouri F, Giraudet AL. Safety and dosimetry of [177Lu]Lu-DOTA-TATE in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours, or pheochromocytomas and paragangliomas: Primary analysis of the Phase II NETTER-P study. Eur J Nucl Med Mol Imaging. 2025 Sep;52(11):4001-4015. doi: 10.1007/s00259-025-07246-7. Epub 2025 Apr 8.

    PubMed 40198358

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lutetium [177Lu] oxodotreotide/dotatate in people with Gastroenteropancreatic Neuroendocrine Tumors and Pheochromocytoma, run by Advanced Accelerator Applications at 7 sites in 5 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 6 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 12 Feb 2026. 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 States, France, Poland, Spain, United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 27 Nov 2024). 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?

Absorbed Radiation Doses in Target Organ (time frame: Up to 8 days after the first Lutetium [Lu 177] dotatate dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04711135, which also lists 1 linked publication.

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 12 Feb 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in