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.
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.
Radiopharmaceutical solution for infusion (7.4 GBq of Lutathera per 30 ml vial)
University of Kentucky
Lexington, Kentucky, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Centre Léon Berard
Lyon, France
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.
Time frame: 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.
Time frame: during first cycle of Lutetium [Lu 177] dotatate treatment (Cycle = 56 days)
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.
Time frame: 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
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.
Time frame: 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
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.
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Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Maria Sklodowska-Curie National Research Institute of Oncology
Gliwice, Poland
Hospital Universitari Vall d'Hebron
Barcelona, Spain
University College Hospital of London
London, United Kingdom
Time frame: 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
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.
Time frame: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose
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.
Time frame: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose
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.
Time frame: Up to 72 hours after the first Lutetium [Lu 177] dotatate dose