Clinical trial NCT06456723: Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.
Official title: Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neuroendocrine Tumors
Keywords: Positron Emission Tomography
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
name: Royal Marsden NHS Foundation Trust
name: University of Manchester
name: The Christie NHS Foundation Trust
name: Invicro
name: Newcastle University
First posted: 2024-06-13
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Radiolabelled somatostatin analogs are invaluable in the diagnosis and treatment of neuroendocrine tumours (NET). The most common positron emission tomography (PET) radiotracers used for the visualisation of NET are radiolabelled somatostatin analogs (SSAs) labelled with \[68Ga\]Ga-DOTA-peptides. However, \[68Ga\]Ga-DOTA-peptide radiolabelled SSAs have significant limitations in terms of accessibility and low throughput. The team at Imperial College London developed a novel radiotracer, \[18F\]fluoroethyl triazole labelled \[Tyr3\]-Octreotate analogue (\[18F\]-FET-βAG-TOCA), in an attempt to overcome these limitations. The FETONET study was designed to have 3 parts. The FETONET study was designed to have 3 parts. Part A evaluated the biodistribution, dosimetry and safety of \[18F\]FET-βAG-TOCA. Uptake was assessed at multiple time points over a 4 hour period. The data was analysed and an optimal imaging time point determined. Part B of the FETONET study involved the performance of whole body static \[18F\]FET-βAG-TOCA PET-CT imaging, at the optimal time point previously established, within a larger cohort of patients. Part C comprised a prospective non-inferiority study that analysed the \[18F\]FET-βAG-TOCA PET/CT data collected within Part A \& Part B and compared this to standard of care \[Ga68\]Ga-DOTA-peptide PET-CT imaging.

Detailed description: Neuroendocrine tumours (NET) are tumours derived from enterochromaffin cells, which are characterised by the expression of somatostatin receptors (SSTRs) on their surface. These tumours release substances into systemic circulation, resulting in episodic flushing, wheezing, diarrhoea, and eventual right-sided valvular heart disease. All of these symptoms negatively impact on patients' quality of life. The management of NET is primarily determined by the stage of disease. For patients with localised or limited disease the primary modality of therapy is surgery. Whilst patients with metastatic disease, undergo systemic therapy with palliative intent. Accurate imaging is therefore central to the management of this disease. Whilst computed tomography (CT) is useful in the localisation of NET, nuclear imaging using tumour-specific radiolabelled receptors are considerably more sensitive and specific methods for detecting NET and their metastases. The most commonly used positron emission tomography (PET) radiotracers used for the visualisation of NET are radiolabelled somatostatin analogs (SSAs) labelled with \[68Ga\]Ga-DOTA-peptides. The \[68Ga\]Ga-DOTA-peptide radiolabelled SSAs have significant limitations in terms of accessibility and low throughput. The team at Imperial College London developed a novel radiotracer, \[18F\]fluoroethyl triazole labelled \[Tyr3\]-Octreotate analogue (\[18F\]-FET-βAG-TOCA), in an attempt to overcome these limitations. The FETONET study was designed to have 3 parts. The FETONET study was designed to have 3 parts. Part A evaluated the biodistribution, dosimetry and safety of \[18F\]FET-βAG-TOCA. Uptake was assessed at multiple time points over a 4 hour period. The data was analysed and an optimal imaging time point determined. Part B of the FETONET study involved the performance of whole body static \[18F\]FET-βAG-TOCA PET-CT imaging, at the optimal time point previously established, within a larger cohort of patients. Part C comprised a prospective non-inferiority study that analysed the \[18F\]FET-βAG-TOCA PET/CT data collected within Part A \& Part B and compared this to standard of care \[Ga68\]Ga-DOTA-peptide PET-CT imaging.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Age ≥ 18 years
* Histological diagnosis of NET of any site, except where ENETS criteria does not mandate histology for confirmation of diagnosis or patients who have a positive 68Gallium-peptide scan in whom NET diagnosis is pre-operatively definitive.
* Locally advanced or metastatic disease.
* Eastern Cooperative Oncology Group (ECOG) performance status of \<2 (appendix A).
* Life expectancy \> 3 months.
* Measurable disease defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥10mm using conventional techniques.
* Somatostatin receptor imaging within 6 months. (if patient does not have somatostatin receptor imaging they may also be included provided they have measurable disease (≥10mm) on conventional imaging.
* Adequate organ system function as defined within Table 1.

Exclusion Criteria:

* Patients received chemotherapy within 3 weeks of study.
* Patients received radiotherapy within 4 weeks of study.
* Active uncontrolled infections, gastrointestinal disease, haemolysis or any serious co-existing medical illness.
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
* Pregnant or lactating women.
* Females of childbearing potential who are unwilling to avoid pregnancy, for the duration of the study.
* Presence of any underlying medical conditions which in the investigators opinion would make the patients unsuitable for treatment.
* Patient not expected to be able to tolerate the scanning sessions.

Primary outcomes:
measure: To Determine the Biodistribution of [18F] Following Single I.V Administration of [18F]-FET-βAG-TOCA Injection in Patients With a Histological Diagnosis of NET.
timeFrame: Baseline (on day of scan over 4 hours)
measure: To Calculate the Effective Dose (ED) of [18F]-FET-βAG-TOCA
timeFrame: Baseline (on the day of the scan over 4 hours)
measure: To Assess Tumoural Uptake of [18F]-FET-βAG-TOCA
timeFrame: Baseline (on the scan day over 4 hours)
Secondary outcomes:
measure: To Compare the Diagnostic Efficacy of [18F]-FET-βAG-TOCA PET/CT With Standard of Care Somatostatin Receptor Imaging in Patients With a Histological Diagnosis of NET.
timeFrame: [68Ga]Ga-DOTA-peptide PET/CT imaging performed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.
measure: Comparison of [18F]-FET-βAG-TOCA PET/CT Scan and Central Review (Nuclear Medicine and Radiology Physician Experts) of All Imaging Received.
timeFrame: [68Ga]Ga-DOTA-peptide PET/CT imaging assessed within 6 months of the [18F]-FET-βAG-TOCA PET/CT scan.
Other outcomes:
Locations:
Study officials:
affiliation: Imperial College London
name: Rohini Sharma
role: STUDY_CHAIR
References:
citation: Dubash SR, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A, Saleem A, Huiban M, Janisch R, Frilling A, Sharma R, Aboagye EO. Clinical Translation of a Click-Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors. J Nucl Med. 2016 Aug;57(8):1207-13. doi: 10.2967/jnumed.115.169532. Epub 2016 May 12.
citation: Dubash S, Barwick TD, Kozlowski K, Rockall AG, Khan S, Khan S, Yusuf S, Lamarca A, Valle JW, Hubner RA, McNamara MG, Frilling A, Tan T, Wernig F, Todd J, Meeran K, Pratap B, Azeem S, Huiban M, Keat N, Lozano-Kuehne JP, Aboagye EO, Sharma R. Somatostatin Receptor Imaging with [18F]FET-betaAG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study. J Nucl Med. 2024 Feb 8;65(3):416-22. doi: 10.2967/jnumed.123.266601. Online ahead of print.