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

Neuroendocrine Tumors Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06455358
• Other study ID #: 2023-02982; th22Nicolas
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: June 2028

Study information

• Verified date: June 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Guillaume Nicolas, Dr.
• Phone: + 41 61 328 66 82
• Email: guillaume.nicolas[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 27
• Est. completion date: June 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

Drug:
• 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.

Other:
• Comparator
Single intravenous administration of 68Ga-DOTA-TOC and PET/CT acquisitions as part of standard clinical care.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Department of Radiology and Nuclear Medicine	Basel	BS

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Optimal injected activity of 61Cu-NODAGA-LM3	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.	1 hour and 3 hours post injection
Other	Tumor detection rate of 61Cu-NODAGA-LM3 PET/CT	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.	1 hour and 3 hours post injection
Other	Correlation of tumor and organ uptake on 61Cu-NODAGA-LM3 PET/CT and quantitated post-treatment SPECT/CT	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.	1 hour and 3 hours post injection
Other	Impact on management of 61Cu-NODAGA-LM3 PET/CT	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.	1 hour and 3 hours post injection
Primary	Frequency of adverse events (number)	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.	from Baseline up to 18 hours post injection
Primary	Severity of adverse events assessed by CTCAE 5.0	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.	from Baseline up to 18 hours post injection
Primary	Assessment of the sensitivity of 61Cu-NODAGA-LM3 PET/CT	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.	1 hour post injection
Secondary	Positive predictive value of 61Cu-NODAGA-LM3 PET/CT	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.	1 hour and 3 hours post injection
Secondary	Dosimetry of 61Cu-NODAGA-LM3	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.)	1 hour, 3 and 18 hours post injection
Secondary	Biodistribution of 61Cu-NODAGA-LM3	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.	1 hour and 3 hours post injection
Secondary	Peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3	The peak plasma concentration (Cmax) of 61Cu-NODAGA-LM3 is determined in 6 patients by serial blood sampling up to max. ~18 h.	Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
Secondary	Blood clearance of 61Cu-NODAGA-LM3	The blood clearance of 61Cu-NODAGA-LM3 is determined in 6 patients by serial blood sampling up to max. ~18 h.	Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
Secondary	Area under the plasma concentration versus time curve (AUC) of 61Cu-NODAGA-LM3	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.	Baseline, 2, 5, 10, 20, and 30 min, 1 hour, 2, 4, and 18 hours post injection
Secondary	Median of the median tumor uptake on 61Cu-NODAGA-LM3 PET/CT	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.	1 hour and 3 hours post injection
Secondary	Median of the mean tumor to background ratio at the best time-point for imaging	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.	1 hour and 3 hours post injection
Secondary	Differential Tumor detection rate	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.	1 hour and 3 hours post injection
Secondary	Mean tumor to background ratio	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.	1 hour and 3 hours post injection
Secondary	Mean signal to noise ratio	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.	1 hour and 3 hours post injection
Secondary	Interreader variability is assessed in terms of sensitivity; number of TP/(TP + FN)	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.	1 hour and 3 hours post injection
Secondary	Patient's preference	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.	Baseline, 1 hour and 3 hours post injection