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

NCT ID: NCT01967537

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 341 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-18
• Study Completion Date: 2018-03-12

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.

Conditions

Neuroendocrine Tumors; Von Hippel-Lindau Syndrome; Hippel-Lindau Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

68Gallium DOTATATE imaging

68Gallium DOTATATE imaging

Group Type: EXPERIMENTAL

68Gallium DOTATATE

Intervention Type: DRUG

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.

Radio-guided surgery

Intervention Type: PROCEDURE

Using 68Gallium DOTATATE

Interventions

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.

Intervention Type: DRUG

Radio-guided surgery

Using 68Gallium DOTATATE

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Naris Nilubol, M.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Naris Nilubol, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22773933 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21349409 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12569593 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0193.html

NIH Clinical Center Detailed Web Page

Other Identifiers

13-C-0193

Identifier Type: -

Identifier Source: secondary_id

130193

Identifier Type: -

Identifier Source: org_study_id