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

Study Overview
=================
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.

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

Conditions
-----------------
GEP-NET, Neuroendocrine Tumors, Neuroendocrine Carcinoma, Neuroendocrine Carcinoma Metastatic

Intervention / Treatment
-----------------
* Drug: 18F-FDG
* Drug: 64Cu-Dotatate


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Each patient will undergo one standard of care 18FDG PET/CT and one 64Cu-DOTATATE PET/CT within 4 weeks. | Drug: 18F-FDG<br>* PET/CT scan approximately 60 min after injection of 18F-FDG<br>* Other names: [18F]F-FDG;Drug: 64Cu-Dotatate<br>* PET/CT scan approximately 60 min after injection of 64Cu-Dotatate<br>* 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 |