Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.

Neuroendocrine Tumors Clinical Trial

— FETONET  

Official title:

Evaluation of [18F]Fluoroethyl Triazole Labelled [Tyr3]-Octreotate Analogues for the Imaging of Neuroendocrine Tumours.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06456723
• Other study ID #: 13HH0807
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 14, 2014
• Est. completion date: October 17, 2018

Study information

• Verified date: June 2024
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radiolabelled somatostatin analogs are invaluable in the diagnosis and treatment of neuroendocrine tumours (NET). 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. Within the FETONET study, two cohorts of patients will undergo PET/CT imaging following an injection of [18F]-FET-βAG-TOCA, with the view to compare the clinical utility of this radiotracer with [68Ga]Ga-DOTA-peptide PET-CT in patients with NET.

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 recruited two cohorts of patients. Patients within Cohort 1 will be consented to undergo whole body dynamic scanning (multiple whole-body scans for up to 3.5 hours) with metabolite analysis, with the view to developing a suitable protocol for static scanning that will be used for patients in Cohort 2. Patients within Cohort 2 will consent to undergo static PET/CT imaging with [18F]-FET-βAG-TOCA, with the view to compare the clinical utility of [18F]-FET-βAG-TOCA-PET/CT with [68Ga]Ga-DOTA-peptide PET/CT (standard of care) in patients with NET.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: October 17, 2018
• Est. primary completion date: October 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

Drug:
• [18F]-FET-ßAG-TOCA
Single I.V. administration of a [18F]fluoroethyl triazole [Tyr3]Octreotate ([18F]-FET-ßAG-TOCA) - maximum injected dose of 370MBq - followed PET/CT imaging.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Imperial College London	Imperial College Healthcare NHS Trust, Invicro, Newcastle University, Royal Marsden NHS Foundation Trust, The Christie NHS Foundation Trust, University of Manchester

References & Publications (2)

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 R — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the biodistribution of [18F] following single I.V. administration of [18F]-FET-ßAG-TOCA injection.	Biodistribution of the [18F]-FET-ßAG-TOCA radiotracer following intravenous administration. Biodistribution assessed through the performance of an [18F]-FET-ßAG-TOCA dynamic PET-CT scan.	-30 to 0 days
Primary	To assess tumoural uptake of [18F]-FET-ßAG-TOCA.	The PET-CT images obtained following injection of the [18F]-FET-ßAG-TOCA radiotracer will be analysed to determine tumoural uptake. [18F]-FET-ßAG-TOCA uptake within the tumours identified will be reported as standardised uptake values (SUV).	-30 to 0 days
Secondary	To assess the efficacy of [18F]-FET-ßAG-TOCA-PET/CT in patients with a histological diagnosis of NET and with measurable disease, who have and have not had [68Ga]-DOTA-peptide imaging.	To determine the clinical utility of [18F]-FET-ßAG-TOCA-PET/CT compared with standard of care [68Ga]Ga-DOTA-peptide imaging by comparing the number of lesions detected using each radiotracer in patients with histologically-confirmed NET.	0-6 months