Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors
Condition: Neuroendocrine Tumors; Von Hippel-Lindau Syndrome; Hippel-Lindau Disease
MeSH terms: Neuroendocrine Tumors; Von Hippel-Lindau Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Neuroendocrine tumors (NETs) are rare but have been more common over the past decade. The
      only treatment for NETs is surgery, but most are found when they are too advanced for
      surgery. Researchers are looking for the best way to find NETs earlier, so that surgery can
      be successful. They want to test if the study drug can be used along with imaging devices to
      detect NETs.

      Objectives:

      - To see how well a new experimental imaging agent, 68Gallium-DOTATATE, detects unknown
      primary and metastatic NETs in the gastrointestinal system and pancreas.

      Eligibility:

      - Adults over 10 years old with a suspected NET or family history of NET.

      Design:

        -  Participants will be screened with a medical history and physical exam, and have a blood
           test.

        -  Participants will undergo three scans. For all of these, a substance is injected into
           their body, they lie on a table, and a machine takes images.

        -  A standard computed tomography (CT) scan of the chest, abdomen, and pelvis.

        -  An octreotide scintigraphy Single photon emission computed tomography (SPECT)/CT.

        -  A 68Gallium-DOTATATE positron emission tomography (PET)/CT. The study drug is injected
           into a vein, usually in the arm. Low-dose X-rays go through the body. For about 40
           minutes a large, donut-shaped device takes images of the body. The entire session takes
           90 to 120 minutes.

        -  Researchers will compare images from the three scans.

        -  Participants will have 1 follow-up visit each year for 5 years. At this visit, they will
           have a medical exam, blood taken, and a CT scan.
    

Detailed description: 
      Background:

        -  Neuroendocrine tumors (NETs) are rare malignancies occurring in the gastrointestinal
           tract, islets of the pancreas, lung, adrenal medulla and thyroid C-cells.

        -  Their incidence has increased over the last decade, with an incidence of 6 per 100,000
           persons a year and they represent 0.46% of all malignancies.

        -  Most NETs are sporadic, but they can be part of familial cancer syndromes such as
           multiple endocrine neoplasia type 1 (MEN1), MEN2, and neurofibromatosis type 1 (NF1) or
           Von Hippel-Lindau (VHL) syndrome.

        -  Surgical resection remains the only curative treatment option for patients with NETs but
           80% of patients are diagnosed with advanced (metastatic, locally inoperable, or
           recurrent) disease.

        -  The main prognostic factor in patients with NET is the extent of disease.

        -  The best imaging technique for detecting unknown primary and metastatic NETs has yet to
           be determined.

        -  NET cells express somatostatin receptors that can be targeted with radiolabeled
           68Gallium-DOTATATE (Octreotate) for imaging purposes.

        -  The primary goal of this protocol is to determine the accuracy of a new somatostatin
           receptor targeted imaging technique, using 68Gallium-DOTATATE PET/CT to detect unknown
           primary and metastatic NETs.

      Objectives:

      -To determine the accuracy of 68Gallium-DOTATATE PET/CT scans in detecting unknown primary
      and metastatic gastrointestinal and pancreatic neuroendocrine tumors.

      Eligibility:

        -  Patients with:

             -  suspicion of NET on axial imaging (CT/magnetic resonance imaging
                (MRI)/fluorodeoxyglucose-positron emission tomography (FDG PET) and/or

             -  biochemical evidence of NET (serum/urinary) based on elevated levels of
                chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive
                intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin,
                catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin),
                glucagon and/or

             -  familial predisposition to NET in patients with multiple endocrine neoplasia type 1
                (MEN1) and VHL.

        -  Age greater than or equal to 18 years of age.

        -  Patients must be willing to return to National Institutes of Health (NIH) for follow-up.

      Design:

        -  Prospective study.

        -  A 68Ga-DOTATATE PET/CT scan will be done in patients with suspicious lesions, unknown
           primary tumor or metastatic gastrointestinal or pancreatic neuroendocrine disease found
           on anatomic imaging (CT/MRI) or in patients having biochemically active disease.

        -  Both functional and non-functional solid tumors will be included in this study.
           Furthermore, asymptomatic and symptomatic, sporadic and familial cases of NETs (such as
           Von Hippel-Lindau (VHL), MEN1) will be included.

        -  Demographic, clinical and pathologic data will be collected from the medical record and
           patient interview for each patient. Data will be stored in a computerized database.

        -  After their initial on-study evaluation, patients will be staged according to findings
           on imaging studies with respect to primary tumor site, size and metastases. Surgical
           resection of NET and/or medical managements will be recommended based on standard
           practice guidelines. In patients who undergo surgical treatment, the samples will be
           immediately stored until molecular analysis.

        -  Follow up will be done yearly for a total duration of 5 years. This includes a yearly
           imaging study and a biochemical and clinical evaluation, to assess tumor growth and
           disease progression.

        -  We estimate that the accrual rate will be 3-10 patients per month; the total accrual
           period for this study will be 10 months to 3 years.
    

Intervention name(s): 68Gallium DOTATATE; Radio-guided surgery
Intervention type(s): Drug; Procedure
Intervention description(s): Fasting is not required prior to the imaging study. An IV line with a large bore (21 gauge or more) will be placed preferably in the antecubital vein, and, with the patient supine, around 5mCi of the 68Ga-DOTATATE will be administered intravenously, followed by incubation for approximately 60 minutes. Then the patient will be positioned in a PET/CT scanner and images from the upper thighs to the base of the skull will be obtained. In patients with tumor induced osteomalacia, images from the top of the head to the toes will be obtained.; Using 68Gallium DOTATATE
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: NET; MEN1; Von Hippel Lindau (VHL); Surgical Resection; Somatostatin Receptor Status