Clinical trial NCT06455358: 61Cu-NODAGA-LM3 PET/CT for the Detection of Neuroendocrine Tumors (COPPER PET in NET)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuroendocrine Tumors
Keywords: Radiolabeled somatostatin receptor ligands
SST PET/CT imaging
somatostatin receptor subtype 2 (SST2)
Tumor detection
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Frequency of adverse events (number)
timeFrame: from Baseline up to 18 hours post injection
measure: Severity of adverse events assessed by CTCAE 5.0
timeFrame: from Baseline up to 18 hours post injection
measure: Assessment of the sensitivity of 61Cu-NODAGA-LM3 PET/CT
timeFrame: 1 hour post injection
Secondary outcomes:
measure: Positive predictive value of 61Cu-NODAGA-LM3 PET/CT
timeFrame: 1 hour and 3 hours post injection
measure: Dosimetry of 61Cu-NODAGA-LM3
timeFrame: 1 hour, 3 and 18 hours post injection
measure: Biodistribution of 61Cu-NODAGA-LM3
timeFrame: 1 hour and 3 hours post injection
measure: Peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3
timeFrame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
measure: Blood clearance of 61Cu-NODAGA-LM3
timeFrame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
measure: Area under the plasma concentration versus time curve (AUC) of 61Cu-NODAGA-LM3
timeFrame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
measure: Median of the median tumor uptake on 61Cu-NODAGA-LM3 PET/CT
timeFrame: 1 hour and 3 hours post injection
measure: Median of the mean tumor to background ratio at the best time-point for imaging
timeFrame: 1 hour and 3 hours post injection
measure: Differential Tumor detection rate
timeFrame: 1 hour and 3 hours post injection
measure: Mean tumor to background ratio
timeFrame: 1 hour and 3 hours post injection
measure: Mean signal to noise ratio
timeFrame: 1 hour and 3 hours post injection
measure: Interreader variability is assessed in terms of sensitivity; number of TP/(TP + FN)
timeFrame: 1 hour and 3 hours post injection
measure: Patient's preference
timeFrame: Baseline, 1 hour and 3 hours post injection
Other outcomes:
measure: Optimal injected activity of 61Cu-NODAGA-LM3
timeFrame: 1 hour and 3 hours post injection
measure: Tumor detection rate of 61Cu-NODAGA-LM3 PET/CT
timeFrame: 1 hour and 3 hours post injection
measure: Correlation of tumor and organ uptake on 61Cu-NODAGA-LM3 PET/CT and quantitated post-treatment SPECT/CT
timeFrame: 1 hour and 3 hours post injection
measure: Impact on management of 61Cu-NODAGA-LM3 PET/CT
timeFrame: 1 hour and 3 hours post injection
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Radiology and Nuclear Medicine
state: BS
Study officials:
affiliation: Division of Nuclear Medicine, University Hospital Basel
name: Guillaume Nicolas, Dr.
role: PRINCIPAL_INVESTIGATOR
References: