Dual 64Cu-DOTATATE and 18F-FDG PET/CT Imaging of Patients With Neuroendocrine Neoplasms

Phase 2

• Conditions: GEP-NET; Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Carcinoma Metastatic
• Interventions: Drug: 18F-FDG; Drug: 64Cu-Dotatate

• Registration Number: NCT05709171
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

Prospective clinical trial investigating combined, dual 18F-FDG PET/CT and 64Cu-DOTATATE PET/CT imaging of patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN)

Detailed Description

Patients with neuroendocrine neoplasms (NEN) represent a heterogeneous disease group with variable prognosis. NEN most frequently arise from the gastrointestinal tract or the pancreas; collectively termed GEP-NEN. Grading of GEP-NEN is based on tumor proliferation index (Ki-67) from biopsies or surgical resection specimens into: low grade G1 neuroendocrine tumor (NET) (Ki-67\<3%), intermediate grade G2 NET (Ki-67 3-20%) and high grade NEN (Ki-67%\>20). High grade NENs are further categorized according to tissue morphology into well-differentiated G3 neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC).

A common feature of most NETs is the overexpression of somatostatin receptors (SSR) on the tumor cell surface. Whole-body PET/CT imaging with radiolabelled SSR-targeted tracers, e.g. 64Cu-DOTATATE, plays a key role in diagnosis, staging, treatment selection and response evaluation of patients with NET. Measurements of 64Cu-DOTATATE tumor standardized uptake values (SUV) and tumor volume on PET/CT provide prognostic value for patients with NET. Patients with high grade NEN often have lower SSR expression and SSR PET/CT is infrequently routinely performed in these patients. However, we expect that the SUV and tumor volume from 64Cu-DOTATATE PET/CT also holds prognostic information for patients with high grade NEN and that some patients may prove eligible for PRRT based on the scans.

18F-FDG PET/CT imaging is widely used in cancers, but is routinely primarily reserved for patients with high grade NEN. However, 18F-FDG PET/CT also holds prognostic information for patients with lower grade NET.

By combining 64Cu-DOTATATE PET/CT and 18F-FDG PET/CT imaging, we expect to obtain complementary prognostic information for patients with GEP-NEN of all grades. In this clinical trial, we will therefore investigate and compare the tumor phenotypes found on 64Cu-DOTATATE PET/CT and 18FDG PET/CT performed within 4 weeks in patients with GEP-NET G1-3 and GEP-NEC. The aim of the trial is to establish prognostic models for progression-free-survival (PSF) and overall survival (OS) including tumor status (positive/negative), SUV measurements, and tumor volume derived from the dual 64Cu-DOTATATE PET/CT and 18FDG PET/CT scans.

Study Timeline

• Study Start: 2023-01-17
• Study First Submitted: 2023-01-24
• Study First Submitted QC: 2023-01-24
• Study First Posted: 2023-02-02
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-22
• Primary Completion: 2025-01-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Histopathologically verified gastro-entero-pancreatic neuroendocrine neoplasm (GEP-NEN) or patients with unknown primary tumor with metastases with verified NEN positive histopathological examination suggesting GEP origin
• World Health Organization (WHO) Performance status 0-2
• Must be able to read and understand the patient information in Danish and to give informed consent

Exclusion Criteria

• Pregnancy
• Breast-feeding
• Weights more than the maximum weight limit for the PET/CT bed of the scanner (140 kg)
• Uncontrolled diabetes
• Uncontrolled infection
• Exacerbation in autoimmune diseases
• Other active cancer disease
• Conditions or diseases (e.g. uncontrolled Parkinson's disease) making the patient unable to lie still in the scanner
• Severe claustrophobia
• Localized neuroendocrine neoplasms of the appendix, the rectum measuring < 1 cm, and ECL-omas of the stomach
• History of allergic reaction attributable to compounds of similar chemical or biologic com-position to 18FDG or 64Cu-DOTATATE

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	64Cu-Dotatate	Each patient will undergo one standard of care 18FDG PET/CT and one 64Cu-DOTATATE PET/CT within 4 weeks.
Experimental	18F-FDG	Each patient will undergo one standard of care 18FDG PET/CT and one 64Cu-DOTATATE PET/CT within 4 weeks.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	12 months after last-patients-last-visit	Time to disease progression from PET/CT scans. Disease progression is defined as a composite measure (whichever occurs first) of RECIST-1.1 defined radiological progression, commencement of another systemic therapy and/or surgery/embolization/ablation related to worsening to the patient's disease status after the index scan, progression evaluated by a multidisciplinary tumor board, and death related to the patient's NEN disease. In case of uncertainty if progression has occurred, the patient's disease status will be evaluated by a multidisciplinary tumor board.

Secondary Outcome Measures

Name	Time	Method
Correlation between tumor standardized uptake values (SUV) on 18F-FDG PET and 64Cu-DOTATATE PET	12 months after last-patients-last-visit	SUV measured on matched tumors on 18F-FDG PET and 64Cu-DOTATATE PET are compared
Overall survival (OS)	12 months after last-patients-last-visit	Time to death from PET/CT scans.
Proportion of patients eligible for peptide receptor radionuclide therapy (PRRT)	12 months after last-patients-last-visit	The proportion of patients who are considered eligible for PRRT based on their 64Cu-DOTATATE PET/CT according to the routine clinical guidelines at the department

Trial Locations

Locations (1)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark