NCT Number: NCT06455358
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.
Interested in participating?
Request Info18 year and older
All sexes
Interventional
Phase 1 / Phase 2
Basel, Canton of Basel-City, 4031, Switzerland
Location status: Recruiting
Damian Wild, Prof. Dr. Dr.
CONTACT
Guillaume Nicolas, Dr.
CONTACT
Guillaume Nicolas, Dr.
PRINCIPAL_INVESTIGATOR
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.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Single intravenous administration of 68Ga-DOTA-TOC and PET/CT acquisitions as part of standard clinical care.
Other names: 68Ga-DOTA-TOC
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 1 hour and 3 hours post injection
The sensitivity of 61Cu-NODAGA-LM3 PET/CT acquired ~ 1h and ~ 3h p.i. is compared with that of the standard of care 68Ga-DOTA-TOC PET/CT acquired ~1h p.i. in the same patients.
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.
Time frame: 1 hour, 3 and 18 hours post injection
Whole body and healthy organ absorbed dose (Gy) is determined in 6 patients by acquiring 3 time-point PET/CT imaging (~1h, ~3 and ~18h p.i.)
Time frame: 1 hour and 3 hours post injection
Tracer uptake distribution in organs is assessed in 6 patients visually and quantitatively (organ SUVmax, SUVpeak and SUVmean) on 61Cu-NODAGA-LM3 PET/CT scans acquired at ~1h and ~3h p.i.
Time frame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
The peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3 is determined in 6 patients by serial blood sampling up to max. ~18 h.
Time frame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
The blood clearance of 61Cu-NODAGA-LM3 is determined in 6 patients by serial blood sampling up to max. ~18 h.
Time frame: Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
The area under the plasma concentration versus time curve (AUC) of 61Cu-NODAGA-LM3 is determined in 6 patients by serial blood sampling up to max. ~18 h.
Time frame: 1 hour and 3 hours post injection
The median of the mean tumor uptake (SUVmax) on 61Cu-NODAGA-LM3 PET/CT is determined at the best time-point for imaging and in comparison with 68Ga-DOTA-TOC PET/CT 1h p.i. for matched lesions only.
Time frame: 1 hour and 3 hours post injection
The median of the tumor to background ratio on 61Cu-NODAGA-LM3 PET/CT at the best time-point for imaging is compared with 68Ga-DOTA-TOC PET/CT 1h p.i. for matched lesions only.
Time frame: 1 hour and 3 hours post injection
To determine the optimal imaging time-point, the difference between the tumor detection rate of 61Cu-NODAGA-LM3 PET/CT at ~1h and at ~3h p.i. is evaluated.
Time frame: 1 hour and 3 hours post injection
To determine the optimal imaging time-point, the mean of the tumor to background ratio of 61Cu-NODAGA-LM3 PET/CT performed ~1h and ~3h p.i. is compared for matched lesions only.
Time frame: 1 hour and 3 hours post injection
To determine the optimal imaging time-point, the mean signal to noise (SNR= SUVmax in Tumor VOI / Standard deviation in background VOI) of 61Cu-NODAGA-LM3 PET/CT is performed ~1h and ~3h post-injection for matched lesions only.
Time frame: 1 hour and 3 hours post injection
To determine the optimal imaging time-point, the interreader variability is assessed in terms of sensitivity (sensitivity = number of true positive (TP) divided by the number of true positive and number of false negative (FN)) of 61Cu-NODAGA-LM3 PET/CT (1 vs 3 h p.i) and 68Ga-DOTATOC PET/CT is evaluated.
Two independent blinded readers will assess the sensitivity of PET/CTs on a dedicated reading workstation using the software MIM Version 7.3.3.
Time frame: Baseline, 1 hour and 3 hours post injection
To determine the optimal imaging time-point, the patient's preference is integrated by using a stress thermometer asking the patient to score their experience between the injection and scanning, and during scanning on a visual analogue scale, ranging from 0: not burdened at all to 10: extremely burdened.
Time frame: 1 hour and 3 hours post injection
The optimal 61Cu-NODAGA-LM3 activity is determined by reconstructing the list-mode PET data for different acquisition frame duration. Signal-to-noise ratios are calculated for lung, pancreas, liver and small intestine as well as for at least one tumor lesion for matched lesions only.
Time frame: 1 hour and 3 hours post injection
Tumor detection rate of 61Cu-NODAGA-LM3 PET/CT in 68Ga-DOTATOC PET/CT negative but NETest-positive NET patients is determined in max. 5 patients.
Time frame: 1 hour and 3 hours post injection
To correlate tumor and organ uptake visible on 61Cu-NODAGA-LM3 PET/CT and quantitated post-treatment SPECT/CT after targeted radionuclide therapy is attempted for 5 patients max.
Time frame: 1 hour and 3 hours post injection
To determine the impact on the clinical management of 61Cu-NODAGA-LM3 PET/CT in SST2-positive tumors, an analysis of pre-defined key imaging findings that may change the intended clinical management by tumor board decision is performed.
Contact information is provided by the study sponsor or research team.
Damian Wild, Prof. Dr. Dr.
CONTACT
Guillaume Nicolas, Dr.
CONTACT
University Hospital, Basel, Switzerland
Other
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
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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