Evaluation of Safety and Dosimetry of Lutetium (177Lu) Oxodotreotide in Adolescent Patients with SSTR-Positive GEP-NETs, Pheochromocytoma, and Paragangliomas
- Trial ID
- 2023-507444-37-00
- Protocol
- CAAA601A32201
Trial statistics
Objectives
The primary objectives of this study are to evaluate the **organ absorbed radiation doses** from peptide receptor radionuclide therapy (PRRT) with Lutathera in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pheochromocytoma, and paragangliomas (PPGLs) as a pooled cohort, and to assess the safety and tolerability of Lutathera in this population. These objectives are clinically relevant as they aim to determine the appropriate dosing and safety profile of Lutathera, which is crucial for optimizing treatment outcomes and minimizing adverse effects in this specific patient group.
Secondary objectives include:
- Evaluating the cumulative safety of Lutathera in adolescents with SSTR-positive GEP-NETs and PPGLs as a pooled cohort.
- Assessing the long-term safety of Lutathera in the same patient population.
- Performing a comparative assessment of dosimetry and pharmacokinetics between adolescent patients with GEP-NETs and PPGLs as a pooled cohort and adult patients using the extrapolation model developed for the clinical study.
Participants
The clinical trial involves a total of **6 participants** diagnosed with **somatostatin receptor positive gastroenteropancreatic neuroendocrine (GEP-NET) tumors, pheochromocytoma, and paragangliomas**. The study population comprises adolescents aged **12 to less than 18 years**. Both **male and female** subjects are included, and the trial specifically targets a vulnerable population. Participants were selected based on the presence of metastasized or locally advanced, inoperable, histologically proven GEP-NET or PPGL, with a confirmed expression of somatostatin receptors. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The health status of participants is assessed using the Karnofsky score or Lansky Play-Performance Scale, with a minimum required score of 50. The selection process ensures that participants and their guardians understand and consent to the study requirements, adhering to local regulations.
Plans and Procedures
The clinical trial is designed to evaluate the **safety** and dosimetry of **Lutathera** in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pheochromocytoma, and paragangliomas. This is a multicenter, open-label study with a phase 4 trial category. The trial will involve a pooled cohort of adolescents aged 12 to less than 18 years, with a focus on assessing organ absorbed radiation doses and the incidence of adverse events. The trial is expected to run from September 8, 2022, to January 9, 2029, with participant involvement lasting up to 36 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as the presence of metastasized or locally advanced, inoperable GEP-NETs or PPGLs, and the expression of somatostatin receptors. The screening will also include performance status assessment and informed consent procedures. Following the initial visit, participants will receive **Lutathera** via intravenous infusion, with follow-up visits scheduled to monitor safety, tolerability, and dosimetry outcomes. The primary endpoints include measuring target organ absorbed radiation doses and recording adverse events post-administration. Secondary endpoints will assess adverse events up to 6 months after the last dose and during a long-term follow-up of 5 years.
The trial will include regular follow-up visits to evaluate short-term and long-term safety, with the end-of-study visit marking the conclusion of participant involvement. Conditions that may lead to early termination from the study include significant adverse events or withdrawal of consent. The trial aims to provide comprehensive data on the safety profile and dosimetry of **Lutathera** in the specified adolescent population, contributing valuable insights into its therapeutic application for these rare conditions.
Treatment
The clinical trial involves the administration of **Lutathera** (lutetium (177Lu) oxodotreotide), a radiopharmaceutical product formulated as a **solution for infusion**. Lutathera is administered intravenously, with a maximum daily dose of 7.4 GBq and a total maximum dose of 29.6 GBq over the treatment period. The treatment duration is set for a maximum of 36 months. Lutathera is specifically relabeled for clinical trial use, and its administration is intended to evaluate the safety and dosimetry in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pheochromocytoma, and paragangliomas. The product is manufactured by Advanced Accelerator Applications and is classified under the ATC code V10XX04.
In addition to Lutathera, the trial includes the administration of **LysaKare**, a solution for infusion containing **L-lysine hydrochloride** and **L-arginine hydrochloride**. This auxiliary treatment is also administered intravenously, with a maximum daily dose of 1000 mL and a total maximum dose of 4000 mL over the treatment period, which is consistent with the 36-month maximum treatment duration. LysaKare is relabeled for clinical trial purposes by Fisher Clinical Services GmbH. The inclusion of LysaKare aims to support the primary treatment with Lutathera, ensuring the safety and tolerability of the therapeutic regimen. The product is also manufactured by Advanced Accelerator Applications and is classified under the ATC code V03AF11.
Efficacy
Efficacy in this clinical trial will be assessed through the evaluation of **target organ absorbed radiation doses** and the incidence of adverse events (AEs) and laboratory toxicities in adolescent patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and pheochromocytoma and paragangliomas (PPGLs). The primary endpoints include measuring the absorbed radiation doses in organs such as the kidney and bone marrow, as well as monitoring the incidence of AEs and laboratory toxicities following the first administration of Lutathera. Secondary endpoints will focus on the incidence of AEs and laboratory toxicities up to six months after the last dose, and during a long-term follow-up period of five years. Additionally, the study will calculate organ absorbed doses and pharmacokinetic parameters based on imaging and blood radioactivity concentration data, comparing these to predicted distributions and organ absorbed doses.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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. 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.
Exclusion Criteria
- 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 (female pediatric patients who are menarchal or who become menarchal during the study), unless they are using highly effective methods of contraception during treatment and for 7 months after the last dose of Lutathera (see details in the Appendix 1). If local regulations deviate from the listed contraception methods to prevent pregnancy, local regulations apply and will be described in the ICF.
- Sexually active male patients, unless they agree to remain abstinent (refrain from heterosexual intercourse) or be willing to use condoms and highly effective methods of contraception with female partners of childbearing potential, and to use condoms with pregnant female partners during the treatment period and for at least 4 months after the last dose of Lutathera (see details in Appendix 1). In addition, male patients must refrain from donating sperm during this same period.
- 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.
- Prior therapies and procedures as detailed in Section 5.2.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 08 Sept 2022 | 2 |
 Poland | Not Recruiting | 08 Sept 2022 | 2 |
 Spain | Not Recruiting | 08 Sept 2022 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
LysaKare 25 g/25 g solution for infusion | Other | SOLUTION FOR INFUSION | INTRAVENOUS USE | 1000 | 36 | PRD7492562 |
Lutathera 370 MBq/mL solution for infusion | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 7.4 | 36 | PRD5434501 |