A Randomized Study of Dosimetry-Based Versus Standard-Dose Peptide Receptor Radionuclide Therapy with Lutetium (177Lu) Edotreotide in Neuroendocrine Tumor Patients

The primary objective of this study is to evaluate whether **dosimetry-based Peptide Receptor Radionuclide Therapy (PRRT)** is more beneficial for patients with **Neuroendocrine Tumors (NETs)** compared to the standard dose PRRT. This investigation is clinically relevant as it aims to optimize treatment efficacy and minimize potential side effects by tailoring the PRRT dose to individual patient needs, potentially improving therapeutic outcomes and quality of life for patients with NETs.

The clinical trial focuses on patients diagnosed with **Neuroendocrine Tumor** (NET), aiming to evaluate the efficacy of dosimetry-based PRRT compared to the standard dose PRRT. The study population includes both male and female participants over the age of 18, with a confirmed diagnosis of neuroendocrine neoplasms (NEN) through histology. Participants must have shown disease progression despite standard treatments or experienced intolerable side effects from such treatments. The trial excludes vulnerable populations and requires participants to have a WHO/ECOG Performance Status of 0-2, a life expectancy greater than six months, and adequate organ function. The sponsor has not provided information regarding the total number of participants. Participants are expected to comply with scheduled visits and study procedures, and written informed consent is mandatory prior to any screening procedures.

The clinical trial is designed to evaluate the efficacy of **dosimetry-based peptide receptor radionuclide therapy (PRRT)** compared to standard dose PRRT in patients with **neuroendocrine tumors (NEN)**. This is a randomized, controlled, double-blind study, conducted over a period of approximately seven years, with an estimated end date of December 24, 2027. The trial involves the administration of **177Lu-DOTATOC** via injection, with a maximum daily dose of 27.5 GBq and a total dose not exceeding 104.5 GBq over a treatment period of up to 48 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, histological confirmation of NEN, and adequate organ function. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety, including assessments of tumor progression, kidney function, and bone marrow function. The primary endpoint is the difference in progression-free survival between the two treatment groups, while secondary endpoints include differences in tumor dose, kidney toxicity, and bone marrow function.

The expected length of participant involvement is up to 48 weeks, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. Participants must demonstrate a willingness and ability to comply with scheduled visits and study procedures, including SPECT/CT scans and laboratory tests. The trial aims to provide insights into whether a tailored dosimetry-based approach to PRRT offers superior outcomes compared to the standard dosing regimen in patients with neuroendocrine tumors.

The clinical trial involves the administration of **177Lu-DOTATOC**, an experimental medication, to patients diagnosed with neuroendocrine neoplasms (NEN). The active substance in this medication is **lutetium (177Lu) edotreotide**, a chemically synthesized compound. The pharmaceutical form of **177Lu-DOTATOC** is an **injection**, and it is administered via the same route. The dosing regimen for this trial includes a maximum daily dose of 27.5 gigabecquerels (GBq) and a cumulative maximum total dose of 104.5 GBq over a treatment period not exceeding 48 weeks. The trial aims to compare dosimetry-based peptide receptor radionuclide therapy (PRRT) with a standard dose PRRT approach.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of **177Lu-DOTATOC**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The trial is designed to evaluate the efficacy and safety of tailored PRRT dosing strategies in improving patient outcomes.

Efficacy in this clinical trial will be assessed by evaluating the **progression-free survival** of patients with neuroendocrine neoplasms (NEN) treated with dosimetry-based peptide receptor radionuclide therapy (PRRT) compared to those receiving standard dose PRRT. The primary endpoint is defined as the time from randomization to documented disease progression or death from any cause, as evaluated by CT scans and RECIST 1.1 criteria.

Secondary endpoints include the difference in tumor dose between the two treatment groups, as well as differences in kidney toxicity, bone marrow function, and subjective side effects. Kidney toxicity will be measured using creatinine levels, estimated glomerular filtration rate (eGFR), cystatin-c, Tc-DTPA clearance, and kidney fibrosis markers such as PRO-6, C3M, and LAMC1. Bone marrow function will be assessed by measuring hemoglobin, white blood cells, and platelet counts. These parameters will be collected and analyzed at specified intervals throughout the trial to determine the efficacy of the treatment regimens.