Clinical trial NCT01967537: Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors
Official title: Evaluation of (68)Gallium- DOTATATE PET/CT for Detecting Primary and Metastatic Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Von Hippel-Lindau Syndrome
Hippel-Lindau Disease
Keywords: NET
MEN1
Von Hippel Lindau (VHL)
Surgical Resection
Somatostatin Receptor Status
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2013-10-23
Enrollment: 341
Sex: ALL
Minimum age (years): 10
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: * INCLUSION CRITERIA:
* Patients with (any one of #1, #2, and/or #3):

  1. Suspicion of neuroendocrine tumors (NET) on axial imaging (computed tomography (CT)/magnetic resonance imaging (MRI)/fluorodeoxyglucose (FDG) positron emission tomography (PET) and/or
  2. biochemical evidence of neuroendocrine tumor (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
  3. familial predisposition to NET in patients with multiple endocrine neoplasia type 1 (MEN1) and Von Hippel-Lindau (VHL) (symptomatic and/or asymptomatic cases; with biochemical or anatomic imaging evidence of disease).
* Age greater than or equal to 10 years of age.
* For females: Negative urine pregnancy test OR post-menopausal for at least 2 years OR patient has had a hysterectomy.
* Patients must be willing to return to National Institutes of Health (NIH) for follow-up.
* Ability of subject or Legally Authorized Representative (LAR) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study.

EXCLUSION CRITERIA:

* Patients unwilling to undergo serial non-invasive imaging.
* Pregnant or lactating women: Pregnant women are excluded from this study because the effects of (68)Ga-DOTATATE in pregnancy are not known. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of

  (68)Ga-DOTATATE in the mother, breastfeeding should be discontinued for at least one day if the mother receives (68)Ga-DOTATATE.
* Patients that have recognized concurrent active infection,
* Patients with the use of any investigational product or device, excluding 18F-dihydroxyphenylalanine (F-DOPA) scans, within 30 days prior to dosing.

Primary outcomes:
measure: Number of Lesions Detected Using the 68Gallium-DOTATATE Positron Emission Tomography (PET/Computed Tomography (CT)) Scan
timeFrame: During PET Scan, up to 2 hours annually for up to 5 years
Secondary outcomes:
measure: Mean Radiation Activity Between Low Grade and Intermediate Grade Neuroendocrine Tumor
timeFrame: During radioguided surgery, up to 2 hours
measure: Tumor Volume of Neuroendocrine Tumors Assessed by the 68Gallium-DOTATATE Scan
timeFrame: During radioguided surgery, up to 2 hours
measure: Median Radioactivity of Tumors With High Expression of Somatostatin Receptor 2 Compared to Tumors With Intermediate Expression of Somatostatin Receptor 2
timeFrame: During PET Scan, up to 2 hours annually
measure: The Number of Tumors Identified in Participants by the Radiation Detector During Radio-guided Surgery Using 68Gallium-DOTATATE
timeFrame: Radio-guided surgery, up to 2 hours
measure: Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
timeFrame: Date treatment consent signed to date off study, approximately 50 months and 17 days.
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Naris Nilubol, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsikitis VL, Wertheim BC, Guerrero MA. Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a seer analysis. J Cancer. 2012;3:292-302. doi: 10.7150/jca.4502. Epub 2012 Jul 1.
citation: Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011 Mar;40(1):1-18, vii. doi: 10.1016/j.ecl.2010.12.005.
citation: Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97(4):934-59. doi: 10.1002/cncr.11105.