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

Overview

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.

Interventions

• 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.

Primary outcome measures

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

Secondary outcome measures (12)

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Diagnostic

Study locations

Switzerland · 1 center

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

Identifiers

NCT: NCT06455358 · 2023-01981; th22Nicolas

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗