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Neuroendocrine TumorsPhase 2NCT01967537

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

A Phase 2 study testing 68Gallium DOTATATE and Radio-guided surgery in people with Neuroendocrine Tumors and Von Hippel-Lindau Syndrome, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 10 to 99 years
What is being tested?
68Gallium DOTATATE and Radio-guided surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
341 participants
Where
1 siteUnited States
Study dates
18 Oct 2013to 12 Mar 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 99 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with (any one of #1, #2, and/or #3):
  • Suspicion of neuroendocrine tumors (NET) on axial imaging (computed tomography (CT)/magnetic resonance imaging (MRI)/fluorodeoxyglucose (FDG) positron emission tomography (PET) and/or
  • 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
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Evaluation of (68)Gallium- DOTATATE PET/CT for Detecting Primary and Metastatic Neuroendocrine Tumors

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.
Read more

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.
Read the 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.
Being tested
68Gallium DOTATATE, Radio-guided surgery
Keywords
NET, MEN1, Von Hippel Lindau (VHL), Surgical Resection, Somatostatin Receptor Status
Medical subject headings
Neuroendocrine Tumors, von Hippel-Lindau Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 68Gallium DOTATATEDrug

    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 surgeryProcedure or surgery

    Using 68Gallium DOTATATE

Study groups in NCT01967537
Study groupRoleWhat they receive
68Gallium DOTATATE imagingExperimental68Gallium DOTATATE imaging
Receives: Drug: 68Gallium DOTATATE; Procedure: Radio-guided surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Lesions Detected Using the 68Gallium-DOTATATE Positron Emission Tomography (PET/Computed Tomography (CT)) Scan

    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.

    Measured: During PET Scan, up to 2 hours annually for up to 5 years

Secondary outcomes (5)
  1. Mean Radiation Activity Between Low Grade and Intermediate Grade Neuroendocrine Tumor

    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.

    Measured: During radioguided surgery, up to 2 hours

  2. Tumor Volume of Neuroendocrine Tumors Assessed by the 68Gallium-DOTATATE Scan

    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.

    Measured: During radioguided surgery, up to 2 hours

  3. Median Radioactivity of Tumors With High Expression of Somatostatin Receptor 2 Compared to Tumors With Intermediate Expression of Somatostatin Receptor 2

    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.

    Measured: During PET Scan, up to 2 hours annually

  4. The Number of Tumors Identified in Participants by the Radiation Detector During Radio-guided Surgery Using 68Gallium-DOTATATE

    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.

    Measured: Radio-guided surgery, up to 2 hours

  5. Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

    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.

    Measured: Date treatment consent signed to date off study, approximately 50 months and 17 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2013 (estimated)
  2. Study start18 Oct 2013
  3. Primary completion17 Dec 2017
  4. Study completion12 Mar 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
341 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01967537
Sponsor's protocol ID
130193
Other IDs
13-C-0193
Status last verified
Nov 2019
First submitted
18 Oct 2013
Last updated
19 Nov 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 22773933
  • 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.

    PubMed 21349409
  • 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.

    PubMed 12569593

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 68Gallium DOTATATE and Radio-guided surgery in people with Neuroendocrine Tumors and Von Hippel-Lindau Syndrome, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01967537, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2019.

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