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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma; Neuroendocrine Carcinoma Metastatic; GEP-NET
• Intervention / Treatment: Drug: 18F-FDG; Drug: 64Cu-Dotatate

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 Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Each patient will undergo one standard of care 18FDG PET/CT and one 64Cu-DOTATATE PET/CT within 4 weeks.	Drug: 18F-FDG; PET/CT scan approximately 60 min after injection of 18F-FDG; Other Names: 18F-fluorodeoxyglucose; fluorodeoxyglucose-F-18; [18F]F-FDG; Drug: 64Cu-Dotatate; PET/CT scan approximately 60 min after injection of 64Cu-Dotatate; Other Names: Copper (64Cu) oxodotreotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	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.	12 months after last-patients-last-visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time to death from PET/CT scans.	12 months after last-patients-last-visit
Correlation between tumor standardized uptake values (SUV) on 18F-FDG PET and 64Cu-DOTATATE PET	SUV measured on matched tumors on 18F-FDG PET and 64Cu-DOTATATE PET are compared	12 months after last-patients-last-visit
Proportion of patients eligible for peptide receptor radionuclide therapy (PRRT)	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	12 months after last-patients-last-visit

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Andreas Kjaer, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 24, 2023
• First Submitted That Met QC Criteria: January 24, 2023
• First Posted (Actual): February 2, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Carcinoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: AK_NEN_DOTA-FDG_21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data are not publicly available due to protection of personal data according to data protection regulations and medical confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No