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Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01967537
Recruitment Status : Completed
First Posted : October 23, 2013
Results First Posted : April 2, 2019
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Naris Nilubol, M.D., National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 18, 2013
First Posted Date  ICMJE October 23, 2013
Results First Submitted Date  ICMJE November 19, 2018
Results First Posted Date  ICMJE April 2, 2019
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE October 18, 2013
Actual Primary Completion Date December 17, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
Number of Lesions Detected Using the 68Gallium-DOTATATE Positron Emission Tomography (PET/Computed Tomography (CT)) Scan [ Time Frame: During PET Scan, up to 2 hours annually for up to 5 years ]
Patients with neuroendocrine tumors (NETs) were scanned with the 68Gallium-DOTATATE Positron Emission Tomography (PET/Computed Tomography (CT)) and the number of lesions detected are collected.
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
To assess the diagnostic accuracy of the new imaging technique (68)Gallium-DOTATATE PET/CT scan for patients with NETs [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2019)
  • Mean Radiation Activity Between Low Grade and Intermediate Grade Neuroendocrine Tumor [ Time Frame: During radioguided surgery, up to 2 hours ]
    The radioactivity was assessed using intraoperative radiation detector following the 68Gallium-DOTATATE injection. Low grade neuroendocrine tumors is defined as tumors with slow cell division determined in histology. Low grade tumors is associated with the best outcome. Intermediate grade tumor is defined as the tumor with medium (3-20%) rate of actively dividing cells and is associated with less favorably outcome.
  • Tumor Volume of Neuroendocrine Tumors Assessed by the 68Gallium-DOTATATE Scan [ Time Frame: During radioguided surgery, up to 2 hours ]
    Participants were scanned using the 68Gallium-DOTATATE Scan. Tumor volume more than 7ml is associated with shorter time to disease progression. Tumor volume more than 36 ml is associated with shorter disease specific survival.
  • Median Radioactivity of Tumors With High Expression of Somatostatin Receptor 2 Compared to Tumors With Intermediate Expression of Somatostatin Receptor 2 [ Time Frame: During PET Scan, up to 2 hours annually ]
    High expression of somatostatin receptor 2 (SSTR2) is based on the intensity grading on immunohistochemistry. High SSTR2 expression may be associated with well-differentiated tumor and high avidity on DOTATATE scan, compared to intermediate or low expression of SSTR that can be seen in poorly differentiated and often aggressive neuroendocrine tumors. Because the correlation can only be from the comparison of preoperative DOTATATE and the tumors that were removed, it is a one time analysis. Subsequent DOTATATE studies are for surveillance and follow up for disease progression or recurrence.
  • The Number of Tumors Identified in Participants by the Radiation Detector During Radio-guided Surgery Using 68Gallium-DOTATATE [ Time Frame: Radio-guided surgery, up to 2 hours ]
    Radio-guided surgery in neuroendocrine tumors using 68Gallium-DOTATATE was performed to detect tumors in the stomach and small bowel neuroendocrine tumors, pancreas, metastatic sites to lymph nodes and liver, and pheochromocytoma or paraganglioma. The number of tumors identified by the radiation detector were assessed.
  • Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) [ Time Frame: Date treatment consent signed to date off study, approximately 50 months and 17 days. ]
    Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors
Official Title  ICMJE Evaluation of (68)Gallium- DOTATATE PET/CT for Detecting Primary and Metastatic Neuroendocrine Tumors
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Neuroendocrine Tumors
  • Von Hippel-Lindau Syndrome
  • Hippel-Lindau Disease
Intervention  ICMJE
  • Drug: 68Gallium DOTATATE
    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.
  • Procedure: Radio-guided surgery
    Using 68Gallium DOTATATE
Study Arms  ICMJE Experimental: 68Gallium DOTATATE imaging
68Gallium DOTATATE imaging
Interventions:
  • Drug: 68Gallium DOTATATE
  • Procedure: Radio-guided surgery
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 14, 2019)
341
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2013)
100
Actual Study Completion Date  ICMJE March 12, 2018
Actual Primary Completion Date December 17, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 99 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01967537
Other Study ID Numbers  ICMJE 130193
13-C-0193
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Naris Nilubol, M.D., National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Naris Nilubol, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP