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

NCT04711135 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: CAAA601A322012020-002951-39EMEA-002950-PIP01-202023-507444-37-00
• Study Type: interventional
• Target: 11
• Locations: 5 countries
• Sites: 7

Brief 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. 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.

Conditions

Pheochromocytoma; Gastroenteropancreatic Neuroendocrine Tumors; Paraganglioma

Keywords

GEP-NET; PPGL; adolescents; pediatric; Lutathera; Lutetium [177Lu] oxodotreotide; Lutetium Lu 177 dotatate; Peptide Receptor Radionuclide Therapy; PRRT

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

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

Secondary Outcomes (6)

• Incidence of Adverse Events (AEs) During Treatment and Short-term Follow-up

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

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

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

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

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

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

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

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

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

Study Arms (1)

GEP-NET and PPGL

EXPERIMENTAL

All 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.

Drug: Lutetium [177Lu] oxodotreotide/dotatate

Interventions

Lutetium [177Lu] oxodotreotide/dotatate DRUG

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

Also known as: Lutathera

GEP-NET and PPGL

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Advanced Accelerator Applications: lead

Study Sites (7)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Centre Léon Berard

Lyon, France

Location

Maria Sklodowska-Curie National Research Institute of Oncology

Gliwice, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

University College Hospital of London

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40198358 DERIVED

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma; Gastro-enteropancreatic neuroendocrine tumor

Interventions

Lutetium; Lutetium-177; copper dotatate CU-64; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-3000

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2020
• First Posted: January 15, 2021
• Study Start: August 31, 2022
• Primary Completion: March 12, 2024
• Study Completion (Estimated): February 6, 2034
• Last Updated: February 12, 2026
• Results First Posted: November 27, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); GB (1); PL (1); US (3); FR (1)