DOTATOC PET/CT for Imaging NET Patients

Study Overview
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Brief Summary
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Neuroendocrine tumours (NETs) are generally slow growing, but some can be aggressive and resistant to treatment. Compared to healthy cells, the surface of these tumor cells has a greater number of special molecules called somatostatin receptors (SSTR). Somatostatin receptor scintigraphy and conventional imaging are used to detect NETs. This study proposes 68Gallium(68Ga)-DOTATOC positron emission tomography/computed tomography (PET/CT) is superior to current imaging techniques. The goal is to evaluate the safety and sensitivity of 68Ga-DOTATOC PET/CT at detecting NETs and other tumors with over-expression of somatostatin receptors.

Detailed Description
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Each subject will have two PET/CT scans, one using 68Ga-DOTATOC and the other using 18-Fluoride-Fluorodeoxyglucose (18F-FDG). The 68Ga-DOTATOC radioactive tracer is manufactured for this study under a Clinical Trial Application filed with Health Canada. 18F-FDG is considered standard care and has been approved by Health Canada. After providing informed written consent subjects will complete a medical history questionnaire. Monitoring of adverse events There will be short-term evaluation of adverse events by comparison of vital signs before and after administration of 68Ga-DOTATOC. Twenty-four hours after 68Ga-DOTATOC administration the study coordinator will call the patient and see if they have experienced any adverse events during that time period and complete the adverse event questionnaire found in section 9.6. Follow-up Assessments The following information will be collected up to 3 years following the PET/CT scans: Initiation of a new treatment Laboratory results and pathology reports Results of imaging studies Final clinical diagnosis by physician and relevant clinical notes The study is expected to take approximately 4 years for accrual.

Official Title
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Evaluation of the Safety and Sensitivity of 68Ga-DOTATOC PET/CT for Imaging NET Patients

Conditions
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Neuroendocrine Tumors, Insulinoma, Gastrinoma, Glucagonoma, Vipoma, Pheochromocytoma, Paraganglioma, Neuroblastoma, Ganglioneuroma, Medullary Carcinoma, Pituitary Adenoma, Medulloblastoma, Merkel Cell Carcinoma, Small-cell Lung Cancer, Meningioma, Carcinoid

Intervention / Treatment
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* Diagnostic Test: 68Ga-DOTATOC PET/CT
* Diagnostic Test: 18F-FDG PET/CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects: World health organization performance status 0-2 Able to provide written informed consent/assent (or consent by guardian for subjects <19 years) Patients must be able to tolerate the physical/logistical requirements of completing a PET scan including lying flat for up to 30 minutes and tolerating intravenous cannulation for injection. Patients must require imaging for either staging or re-staging of: Gastroenteropancreatic tumors (e.g. carcinoids, gastrinoma, insulinoma, glucagonoma, VIPoma, etc.), functioning and non-functioning Sympathoadrenal system tumors (phaeochromocytoma, paraganglioma, neuroblastoma, ganglioneuroma) Medullary thyroid carcinoma Pituitary adenoma Medulloblastoma Merkel cell carcinoma Small-cell lung cancer (mainly primary tumors) Meningioma Or any other NET / with potential for overexpression of SSTR Exclusion Criteria: Pregnancy Patients who are medically unstable ex: acute cardiac or respiratory distress, hypotensive Patients who exceed the safe weight limit of the PET/CT bed (204.5 kg) or who cannot fit through the PET/CT bore (diameter 70cm).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PET/CT Diagnostic Imaging<br>Each subject will have two PET/CT scans, one using 68Ga-DOTATOC and the other using 18F-FDG. The 68Ga-DOTATOC radioactive tracer is manufactured for this study under a Clinical Trial Application filed with Health Canada. 18F-FDG is considered standard care and has been approved by Health Canada. | Diagnostic Test: 68Ga-DOTATOC PET/CT<br>* Blood pressure, heart rate, and oxygen saturation levels will be recorded prior to the injection and at 5 - 15 minutes after injection. Each study subject will have an intravenous catheter inserted. The subject will receive a bolus intravenous dose of the radiotracer from an approved study supplier site. The subject will rest in a comfortable chair for 60 minutes. After this uptake phase, the blood pressure, heart rate, and oxygen saturation levels will be recorded again. The subjects will then be taken to a designated washroom and asked to void prior to being scanned in order to clear excreted radiotracer activity from the urinary tract. Subjects are positioned supine, arms down, and centered on the scanner bed and the PET/CT images will be acquired.<br>Diagnostic Test: 18F-FDG PET/CT<br>* 18F-FDG PET/CT For 18F-FDG as fasting period of 6 hours is required before the scan. Each study subject will have an intravenous catheter inserted. The subject will receive a bolus intravenous dose of the radiotracer from an approved study supplier site. The subject will rest in a comfortable chair for 60 minutes. The subjects will then be taken to a designated washroom and asked to void prior to being scanned in order to clear excreted radiotracer activity from the urinary tract. Subjects are positioned supine, arms down, and centered on the scanner bed and the PET/CT images will be acquired.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of 68Ga-DOTATOC PET/CT in the diagnosis of SSTR positive tumors. | Determination of sensitivity of both exams when compared with pathology reports (if available) and compared with routine imaging (CT, MRI, Octreoscan™, US) if available and will be determined by confidence intervals using an exact binominal distribution by comparing the 68Ga-DOTATOC PET/CT with 18F-FDG and conventional imaging (if available). The gold standard for the detection of lesions will be established through a combination of: 1) pathology; 2) unequivocal correlative imaging results as assessed independently by 2 physicians; 3) disease progression of specific findings upon follow-up, up to three years from baseline examination; 4) a clearly unequivocal plurimetastatic pattern confirmed by any imaging modality at any of the involved sites; 5) response of lesions on subsequent imaging following therapy. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with 68Ga-DOTATOC-related adverse events as assessed by abnormal vital sign measurement. | Vital signs (blood pressure, heart rate and pulse oximetry) will be measured at three time points (before and after injection, and 1 hour after the injection). All values that fall outside of the normal parameters will be assessed by a physician and reported as an adverse event. | 1 hour | 
| Number of participants with self-reported 68Ga-DOTATOC-related adverse event | Patients will be contacted by phone 24 hours after the 68Ga-DOTATOC PET/CT scan to see if they experienced any adverse events. These are recorded and evaluated for severity and likelihood they are related to the study drug. All adverse events will be recorded and summarized in the final report. | 24 hours | 
| Total number of lesions per anatomic location identified by 68Ga-DOTATOC PET/CT | All lesions will be tabulated and classified by compartment (pancreas, liver, bowel, lung and mediastinum, abdomen and retroperitoneal lymph nodes, bone, other) for all imaging modalities that have been done for that subject. A total number of lesions (for all modalities) will be calculated and a proportion of lesions detected by each modality will be reported and will be compared by calculating the median and its confidence interval. This will assess the efficacy of 68Ga-DOTATOC PET/CT. | 3 years |