GEP-NET, Neuroendocrine Tumors, Neuroendocrine Carcinoma, Neuroendocrine Carcinoma Metastatic
Conditions
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.
Interventions
DRUG18F-FDG
PET/CT scan approximately 60 min after injection of 18F-FDG
DRUG64Cu-Dotatate
PET/CT scan approximately 60 min after injection of 64Cu-Dotatate
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 12 months after last-patients-last-visit | Time to death from PET/CT scans. |
| 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 |
| 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 |
Countries
Denmark
Outcome results
None listed