61Cu-NODAGA-LM3 PET/CT for the Detection of Neuroendocrine Tumors (COPPER PET in NET)

Официальное название

61Cu-NODAGA-LM3 PET/CT for the Detection of Neuroendocrine Tumors: The COPPER PET in NET Study A Prospective, Open-label, Randomized, Controlled, Single Centre, Phase I/II PET/CT Study

Обзор

The goal of this monocentric, open-label, randomized-controlled, reader-blind clinical study is to assess the safety of the radiolabeled somatostatin receptor ligand, 61Cu-NODAGA-LM3, and its sensitivity in comparison to the standard of care, 68Ga-DOTATOC, for PET/CT imaging in patients with well differentiated bronchopulmonary and gastroenteropancreatic neuroendocrine tumors.

Подробное описание

Neuroendocrine tumors (NET) originate from neuroendocrine cells and are most commonly found in the gastro-intestinal tract, pancreas and lung. Many NET grow slowly and are asymptomatic, leading to up to 50% being metastatic at diagnosis. Overexpression of somatostatin receptor subtype 2 (SST2) is a characteristic of NET and presents an important molecular target for the management of these tumors.

In Switzerland, two radiolabeled somatostatin analogues, gallium-68-labeled (68Ga)-DOTATOC and 68Ga-DOTATATE, are used for SST PET/CT imaging of well-differentiated neuroendocrine tumors. While these radiolabeled SST agonists provide high clinical performance and can be locally produced, they face limitations such as high costs, limited production capacity, short half-life hindering shipment to smaller centers, and high physiological uptake in organs like the liver, complicating tumor detection.

A novel copper-61 (61Cu) labeled somatostatin receptor antagonist, 61Cu-NODAGA-LM3, shows promise as an imaging agent for SST2 expressing tumors. It offers a longer half-life, enhanced tumor uptake and retention compared to established radiolabeled SST agonists, and improves image contrast.

This study aims to compare the safety and sensitivity of 61Cu-NODAGA-LM3 to the standard of care, 68Ga-DOTATOC, for SST PET/CT imaging in patients with well-differentiated bronchopulmonary and gastroenteropancreatic neuroendocrine tumors.

The results of the study potentially lead to enhanced diagnostic accuracy and patient care in the management of neuroendocrine tumors.

Вмешательства

• Препарат 61Cu-NODAGA-LM3
  Single intravenous administration of 61Cu-NODAGA-LM3 at an amount of 20 -40 μg (or 13 - 26 nmol) and an activity range of 150 MBq (±25%) followed by up to three PET/CT acquisitions.
• Другое Comparator
  Single intravenous administration of 68Ga-DOTA-TOC and PET/CT acquisitions as part of standard clinical care.

Первичные конечные точки

• Frequency of adverse events (number) [Срок оценки: from Baseline up to 18 hours post injection]
• Severity of adverse events assessed by CTCAE 5.0 [Срок оценки: from Baseline up to 18 hours post injection]
• Assessment of the sensitivity of 61Cu-NODAGA-LM3 PET/CT [Срок оценки: 1 hour post injection]

Вторичные конечные точки (12)

• Positive predictive value of 61Cu-NODAGA-LM3 PET/CT [Срок оценки: 1 hour and 3 hours post injection]
• Dosimetry of 61Cu-NODAGA-LM3 [Срок оценки: 1 hour, 3 and 18 hours post injection]
• Biodistribution of 61Cu-NODAGA-LM3 [Срок оценки: 1 hour and 3 hours post injection]
• Peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3 [Срок оценки: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection]
• Blood clearance of 61Cu-NODAGA-LM3 [Срок оценки: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection]
• Area under the plasma concentration versus time curve (AUC) of 61Cu-NODAGA-LM3 [Срок оценки: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection]
• Median of the median tumor uptake on 61Cu-NODAGA-LM3 PET/CT [Срок оценки: 1 hour and 3 hours post injection]
• Median of the mean tumor to background ratio at the best time-point for imaging [Срок оценки: 1 hour and 3 hours post injection]
• Differential Tumor detection rate [Срок оценки: 1 hour and 3 hours post injection]
• Mean tumor to background ratio [Срок оценки: 1 hour and 3 hours post injection]
• Mean signal to noise ratio [Срок оценки: 1 hour and 3 hours post injection]
• Interreader variability is assessed in terms of sensitivity; number of TP/(TP + FN) [Срок оценки: 1 hour and 3 hours post injection]

Критерии участия

Критерии включения

• Written informed consent signed
• >18 years old patients of either gender
• For women in child-bearing age: a negative pregnancy test is required
• Histologically proven well-differentiated bronchopulmonary (typical or atypical carcinoid) or gastroenteropancreatic neuroendocrine tumors (NET) of all grade (including NET G3 with Ki-67 <30 %)
• Clinical indication to somatostatin receptor (SST) PET/CT imaging for either primary staging, restaging, patient selection to Peptide Receptor Radionuclide Therapy, treatment planning or treatment response assessment
• Standard of care 68Ga-DOTATOC PET/CT performed or planned within max. 4 weeks prior or after IMP-administration, as clinically indicated
• At least 3 lesions detected by the previous somatostatin receptor scan, or if 68Ga-DOTATOC PET/CT is negative, a positive NETest not older than 4 weeks should be available in 5 additional patients
• Estimated eGFR (CKD-EPI) ≥ 45 mL/min
• If applicable, the last regular somatostatin analogue injection should be administered 2 weeks +/- 1 week prior to SST PET scan for long acting release forms

Критерии исключения

• Known hypersensitivity to 61Cu, to NODAGA, to LM3 or to any of the excipients of 61Cu-NODAGA-LM3
• Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide used on such radiopharmaceutical including at any time during the current study
• Initiation or continuation of active anti-tumor treatment between 61Cu-NODAGA-LM3 and 68Ga-DOTATOC PET/CT, except continuation of long acting somatostatin analogues
• Presence of active infection at screening or history of serious infection within the previous 6 weeks
• Pregnant or breast-feeding women
• History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Диагностика

Центры проведения

Швейцария · 1 центр

• University Hospital Basel, Department of Radiology and Nuclear Medicine — Basel

Идентификаторы

NCT: NCT06455358 · 2023-01981; th22Nicolas

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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