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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Frequency of adverse events (number)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
61Cu-NODAGA-LM3 PET/CT before 68Ga-DOTATOC PET/CT
Participants randomized into this group undergo 61Cu-NODAGA-LM3 PET/CT between 24 hours to 4 weeks before routine 68Ga-DOTATOC PET/CT.
干预措施: 61Cu-NODAGA-LM3 (Drug)
61Cu-NODAGA-LM3 PET/CT before 68Ga-DOTATOC PET/CT
Participants randomized into this group undergo 61Cu-NODAGA-LM3 PET/CT between 24 hours to 4 weeks before routine 68Ga-DOTATOC PET/CT.
干预措施: Comparator (Other)
61Cu-NODAGA-LM3 PET/CT after 68Ga-DOTATOC PET/CT
Participants randomized into this group undergo 61Cu-NODAGA-LM3 PET/CT between 24 hours to 4 weeks after routine 68Ga-DOTATOC PET/CT.
干预措施: 61Cu-NODAGA-LM3 (Drug)
61Cu-NODAGA-LM3 PET/CT after 68Ga-DOTATOC PET/CT
Participants randomized into this group undergo 61Cu-NODAGA-LM3 PET/CT between 24 hours to 4 weeks after routine 68Ga-DOTATOC PET/CT.
干预措施: Comparator (Other)
结局指标
主要结局
Frequency of adverse events (number)
时间窗: from Baseline up to 18 hours post injection
The safety of 61Cu-NODAGA-LM3 is assessed in a primary safety analysis that is descriptive in nature and is performed in the safety analysis set, including information about the frequency (number) of adverse events.
Assessment of the sensitivity of 61Cu-NODAGA-LM3 PET/CT
时间窗: 1 hour post injection
The sensitivity of 61Cu-NODAGA-LM3 PET/CT acquired \~ 1h p.i. is compared with that of the standard of care 68Ga-DOTA-TOC PET/CT acquired \~1h p.i.. Sensitivity is determined based on the adjudication of all suspected lesions (union of the sets of lesions detected by two blinded independent readers) against a gold standard. The gold standard is defined either as a biopsy whenever possible and if clinically indicated or a comparison to the best imaging modality for the patient given case 2 - 7 months during follow up. After all "true" lesions are identified on all images, it is determined whether or not a given lesion has been identified on the 61Cu-NODAGA-LM3 PET/CT and on the 68Ga-DOTA-TOC PET/CT scans.
Severity of adverse events assessed by CTCAE 5.0
时间窗: from Baseline up to 18 hours post injection
The safety of 61Cu-NODAGA-LM3 is assessed in a primary safety analysis that is descriptive in nature and is performed in the safety analysis set, including information about the severity of adverse events. Severity will be graded as per CTCAE (Common Terminology Criteria for Adverse Events) Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting ageappropriate instrumental ADL (Activities of Daily Living). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
次要结局
- Mean signal to noise ratio(1 hour and 3 hours post injection)
- Biodistribution of 61Cu-NODAGA-LM3(1 hour and 3 hours post injection)
- Positive predictive value of 61Cu-NODAGA-LM3 PET/CT(1 hour and 3 hours post injection)
- Median of the median tumor uptake on 61Cu-NODAGA-LM3 PET/CT(1 hour and 3 hours post injection)
- Median of the mean tumor to background ratio at the best time-point for imaging(1 hour and 3 hours post injection)
- Area under the plasma concentration versus time curve (AUC) of 61Cu-NODAGA-LM3(Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection)
- Dosimetry of 61Cu-NODAGA-LM3(1 hour, 3 and 18 hours post injection)
- Peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3(Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection)
- Mean tumor to background ratio(1 hour and 3 hours post injection)
- Patient's preference(Baseline, 1 hour and 3 hours post injection)
- Blood clearance of 61Cu-NODAGA-LM3(Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection)
- Differential Tumor detection rate(1 hour and 3 hours post injection)
- Interreader variability is assessed in terms of sensitivity; number of TP/(TP + FN)(1 hour and 3 hours post injection)