Single Microdose Trial- CXCR4 PET Tracer - Pharmacokinetics and Pharmacodynamics of [68Ga]Ga-R54, a Radiopharmaceutical Directed Toward CXCR4 in Patients With Advanced Solid Neoplasia.

Обзор

Phase 1, monocentric, open labeled, no profit "Microdose" trial. A single microdose of the new \[68Ga\]Ga-R54 PET radiopharmaceutical directed against CXCR4 will be injected into patients with advanced solid tumor or multiple myeloma to evaluate the binding.

Подробное описание

The present study aims to evaluate the pharmacokinetic/pharmacodynamic profile and the engagement capacity of a new PET probe that binds the CXCR4 receptor. A Microdose-Trial (Guideline ICH M3(R2) CPMP/ICH/286/95 type 1 approach and EMEA/CHMP/SWP/28367/07 Rev. 1) is proposed in order to evaluate the pharmacokinetics and pharmacodynamics of a single microdose of the radiopharmaceutical \[68Ga\]Ga-R54 in patients suffering from solid tumors in the advanced stage of the disease or multiple myeloma. At least 5 and no more than 10 consenting patients with advanced solid tumors (breast, lung, colon, ovary, and pancreas) or multiple myeloma will be recruited with at least 1 patient per pathology whose neoplasm expresses CXCR4. Study patients will receive i.v. a single dose of \[68Ga\]Ga-R54 ≤100 μg. The localization of the target will be carried out with PET/CT method. Pharmacokinetics will be analyzed by blood samples taken at 2, 5, 10, 30 minutes, 1, 2 and 4 hours post infusion. Patients will be enrolled at least 7 days apart to monitor the onset of adverse events.

Вмешательства

• Препарат [68Ga]Ga-R54 PET/CT
  A single intravenous microdose (≤100 μg) of the CXCR4-targeting radiopharmaceutical \[68Ga\]Ga-R54 is administered, followed by whole-body PET/CT imaging. Serial blood samples are collected up to 4 hours post-injection to assess pharmacokinetics. Imaging is performed according to institutional standards to evaluate in vivo CXCR4 expression in tumor lesions.

Первичные конечные точки

• Quantitative analysis of the uptake (pharmacodynamics) of [68Ga]Ga-R54 in the neoplastic lesion by measuring the "maximum standardized uptake value" (SUVmax). [Срок оценки: Single time point at PET/CT imaging (Day 1)]
• Pharmacokinetics of the PET radiopharmaceutical [68Ga]Ga-R54 through measurement of radioactivity in blood at the gamma counter (%ID/g). [Срок оценки: Peri-procedural (at time of PET/CT imaging, Day 1)]

Вторичные конечные точки (2)

• Evaluation of the dosimetric parameters for the tumor and for healthy organs by determining the absorbed dose per unit of activity administered (mGy/MBq). [Срок оценки: From time of [68Ga]Ga-R54 administration up to 4 hours post-injection]
• SUVmax correlation of the radiopharmaceutical [68Ga]Ga-R54 and CXCR4 expression assessed by immunohistochemistry in the tumor and microenvironment. [Срок оценки: Single time point at PET/CT imaging (Day 1)]

Критерии участия

Критерии включения

• Patients > 18 years
• Patients with histological diagnosis of solid neoplasm (breast, lung, colon, ovary, pancreas) in advanced stages or multiple myeloma evaluated by PET/CT with \[18F\]FDG carried out in the 3 months prior to enrollment. The neoplasm must express the CXCR4 receptor by immunohistochemistry
• Patients with ECOG performance status 0-2, able to undergo the scheduled diagnostic procedure (PET/CT with \[68Ga\]Ga-R54).
• Patients with alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase <3 x upper limit of reference range and total bilirubin <2.0 mg/dL
• Patients with creatinine < 1.5 x upper limit of reference range or 24-hour creatinine clearance > 50 mL/min
• Negative serum pregnancy test (b-hCG) for women of childbearing age before administration of \[68Ga\]Ga-R54).
• Signature of informed consent indicating that the patient (or legal representative) has been informed of all aspects pertinent to the study
• Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures.

Критерии исключения

• Presence of active infections (e.g. requiring antibiotic therapy) or other serious concomitant illness, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study
• Declared chronic active hepatitis (hepatitis B / C)
• Declared active autoimmune diseases
• Recovery from major trauma including surgery within 4 weeks of study enrollment
• Presence of neurodegenerative diseases
• Pregnancy and/or breastfeeding
• Any conditions that in the opinion of the investigator could hinder compliance with the study protocol
• Patients who have not signed consent to participate in the study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Италия · 1 центр

• Istituto Nazionale Tumori Fondazione G. Pascale - SC Medicina Nucleare e Terapia Metabolic — Naples

Идентификаторы

NCT: NCT07577206 · R4 FOUR-PET · 2024-513303-14-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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