Clinical trial NCT04804371: Dual Tracer (68Ga-DOTATATE and 18F-FDG) PET Imaging in G2 & G3 Gastroenteropancreatic Neuroendocrine Tumors
Official title: Combined 68Ga-DOTATATE and 18F-FDG PET/CT Imaging in Patients With Well-differentiated, G2-G3, Gastroenteropancreatic (GEP)-Neuroendocrine Tumors (NETs) - A Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Neuroendocrine Tumors
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Neuroendocrine Tumour Society (CNETS)
First posted: 2021-03-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Histologically proven well diff GEP NET, G2-3, Ki 67 ≥3% (or mitotic index ≥2 mitosis/10HPF).
Primary purpose: DIAGNOSTIC

Brief summary: The variable clinical outcome of patients with G2 \& G3 well diff GEP-NETs makes the selection of an optimal treatment strategy challenging.

Initial data suggests that high DOTATATE uptake and low FDG uptake are suggestive of low grade disease, with an indolent course.

Conversely, low DT uptake and high FDG uptake are suggestive of high-grade/ aggressive disease.

G2/3 GEP NETs may be biologically diverse; clinically relevant cohort for dual-tracer PET imaging.

Our secondary objectives are

1. To determine the distribution of PETNET scores derived from 18F-FDG \& 68Ga-DT PET in patients with G2 \& G3 well diff GEP-NETs.
2. To determine the proportion of patients in whom the addition of 18F-FDG PET data results in a change in planned clinical management.

To assess intra-individual variability in SSTR expression \& glucose metabolism (as seen on DT and FDG PET) across different tumor sites within the same patient.

2) To determine whether a correlation exists between tumor texture features on 68Ga-DT \& FDG PET to tumor grade and Ki 67 index.

3) To assess for an association between tumor texture features on 68Ga-DT PET and glucose metabolism; and/or an association between tumor texture features on FDG PET and SSTR expression.

Detailed description: The variable clinical outcome of patients with G2 and G3 well differentiated GEP-NETs makes the selection of an optimal treatment strategy challenging.

A subject with 68Ga-DOTATATE uptake on all lesions without FDG uptake is likely to have low-grade, metabolically inactive disease, leading to an indolent disease course and may also be a predictive biomarker in subjects being considered for PRRT.

Conversely, avidity on 18F-FDG PET/CT and non-avidity on 68Ga-DOTATATE may indicate a high-grade NET, and would predict resistance to PRRT, suggesting that a more "aggressive" approach with systemic chemotherapy might be beneficial.

Therefore, the prospective assessment of PETNET score in patients with G2 or G3 GEP NETs, which may be biologically diverse is the most clinically relevant group for dual-tracer PET imaging.

Primary Objectives:

1. To determine the distribution of PETNET scores derived from 18F-FDG and 68Ga-DOTATATE PET/CT in patients with G2 and G3 well differentiated GEP-NETs.
2. To determine the proportion of patients in whom the addition of 18F-FDG PET/CT data results in a change in planned clinical management.

Secondary Objectives:

1. mTo determine whether there is intra-individual variability in somatostatin receptor expression and glucose metabolism (as seen on DOTATATE PET and FDG PET, respectively) across different tumor sites within the same patient.
2. To determine whether a correlation exists between tumor texture features on 68Ga-DOTATATE PET and FDG PET to tumor grade and Ki67 index.
3. To assess if an association exists between tumor texture features on 68Ga-DOTATATE PET and glucose metabolism; and/or an association between tumor texture features on FDG PET and somatostatin receptor expression.

Eligibility criteria: Inclusion Criteria:

1. Has provided written informed consent prior to any study-related procedures,
2. Is a male or a female of 18 years of age or older.
3. Patients who already had/scheduled for a 68Ga-DOTATATE PET/CT scan.
4. Has a gastro entero-pancreatic neuroendocrine neoplasm confirmed by histological criteria. Patients with unknown primaries clinically thought to be from gastroenteropancreatic source shall be eligible.
5. Has a well differentiated tumour Grade 2-3 (WHO 2017).
6. Has a tumour with a proliferation index (Ki67 ≥3%) or in samples where the Ki67 antigen cannot be reliably quantified, a mitotic index ≥2 mitosis/10HPF (high power fields)
7. Treatment naïve patients and/or patient who have received any number of prior systemic therapy lines for metastatic disease and/or locally advanced inoperable tumor.
8. Willing and able to comply with all study requirements, including timing and/or nature of required assessments.
9. Women of child-bearing age will undergo a urine test to exclude pregnancy prior to PET.

Exclusion Criteria:

1. Patients with known lung neuroendocrine tumours or other proven non gastroenteropancreatic histologies are not eligible.
2. Patients with any known hypersensitivity to FDG.
3. Has a well differentiated neuroendocrine tumour Grade 1 (WHO 2017).
4. Has a poorly differentiated neuroendocrine carcinoma (WHO 2017).
5. Mixed neuroendocrine and non-neuroendocrine cancer
6. Has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
7. Any patient who is pregnant.

Primary outcomes:
measure: Discordance in tracer uptake:
timeFrame: 2 years
measure: Impact to patient management:
timeFrame: 2 years
Secondary outcomes:
measure: Intraindividual tumor heterogeneity:
timeFrame: 2 years
measure: Tumor texture geatures as predictors of tumor grade:
timeFrame: 2 years
measure: Tumor texture features as predictors of tumor metabolism and somatostatin receptor expression:
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Ur Metser, MD
role: PRINCIPAL_INVESTIGATOR
References: