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Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04074135
Recruitment Status : Recruiting
First Posted : August 29, 2019
Last Update Posted : May 21, 2024
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


People with von Hippel-Lindau (VHL) can have problems with a variety of organs, such as the pancreas. The disease can cause tumors of the pancreas. This can result in life-threatening complications. Researchers want to learn more about these pancreatic tumors and how to better detect them. This may help them design better future treatment and care for people with VHL disease.


To better understand VHL disease that affects the pancreas and to test whether adding a certain type of scan (68-Gallium DOTATATE PET/CT) can further detect tumors.


People ages 12 and older with VHL that causes tumors and cysts to grow in the pancreas


Participants will be screened with their medical records and imaging studies.

Participants will have an initial evaluation:

Participants will have their body examined by different doctors. This will depend on what types of symptoms they have.

Participants will have blood and urine tests

Participants will have images made of their body using one or more machines: They made have a CT or PET/CT scan in which they lie on a table that moves through a big ring. They may have an MRI in which they lie on a table that moves into a big tube. They may have an ultrasound that uses a small stick that produces sound waves to look at the body.

After the first visit, participants will be asked to return to the NIH. Some of the tests performed at the first visit will be repeated. Depending on their disease status, visits will be once a year or every 2 years for life.

Condition or disease Intervention/treatment Phase
VHL Pancreatic Neuroendocrine Tumors Von Hippel-Lindau Disease Neuroendocrine Tumors Drug: 68-Gallium DOTATATE Phase 2

Detailed Description:


  • Patients with the von Hippel-Lindau (VHL) familial cancer syndrome demonstrate manifestations in a variety of organs, including the pancreas. Pancreatic manifestations can range from benign cysts and micro cystic adenomas to neuroendocrine tumors of the pancreas which are capable of regional and distant metastases. These neuroendocrine tumors can result in life-threatening complications.
  • This protocol is designed to identify VHL patients with pancreatic manifestations and to follow these patients with serial imaging studies, germ line genetic analysis, discovery of serum biomarkers, and novel imaging modalities such as 68-Gallium DOTATATE PET/CT scan.


- To comprehensively and longitudinally evaluate the natural history of patients with VHL pancreatic neuroendocrine tumors and cystic lesions, estimating and defining their clinical spectrum.


- Patients greater than or equal to 12 years of age diagnosed with VHL.


  • Demographic data will be collected from the medical record and patient interview for each patient participant. Data will be securely stored in a computerized database.
  • Patients will be evaluated by the urology, neurosurgery, brain oncology and/or ophthalmology personnel as indicated to rule out or manage other manifestations of VHL such as hemangioblastoma, renal cell cancer, and pheochromocytoma.
  • Anatomical and functional clinical imaging studies, research blood and urine sample collection will be performed at each scheduled visit. Research 68-Gallium DOTATATE PET/CT imaging studies in adult subjects will be performed, no more than once per year.
  • Surgical resection of solid lesions of the pancreas will be recommended based on previously published criteria.
  • Based on our analysis of likelihood of tumor growth or risk of metastasis, data will be analyzed every two years and appropriate revisions will be made to the surgical management guidelines, if indicated by data analysis.
  • Projected accrual will be 40 patients per year for a total of 15 years. Considering some patients may have a screen failure, we anticipate accruing of 740 patients on this protocol.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 740 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of the Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors
Actual Study Start Date : June 2, 2020
Estimated Primary Completion Date : January 30, 2036
Estimated Study Completion Date : July 1, 2036

Arm Intervention/treatment
Experimental: 1/ Arm 1
Study natural history of VHL pancreatic neuroendocrine tumors with yearly 68-Gallium DOTATATE PET/CT research scans.
Drug: 68-Gallium DOTATATE
68-Gallium DOTATATE, to be used in yearly PET/CT research scans

No Intervention: 2/ Arm 2
Study natural history of VHL pancreatic neuroendocrine tumors without research scans.

Primary Outcome Measures :
  1. Characterization of the natural and clinical histories of VHL pancreatic neuroendocrine tumors and cystic lesions [ Time Frame: 15 years ]
    Characterization of the natural and clinical histories of VHL pancreatic neuroendocrine tumors and cystic lesions

Secondary Outcome Measures :
  1. predictive value of 68-Gallium DOTATATE PET/CT imaging in patient population [ Time Frame: at each scheduled visit ]
    mean uptake between these two groups of adult patients in which per patient uptake is defined as the average uptake of multiple lesions detected in each patient

  2. growth rate in solid pancreatic tumors [ Time Frame: at each scheduled visit ]
    graded tumor biopsy

  3. distribution of time from initial presentation with pancreatic tumors to the time that surgery is recommended [ Time Frame: at each scheduled visit, until surgery is recommended ]
    median amount of time from initial presentation with pancreatic tumors to the time that surgery is recommended

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. Subjects who have been diagnosed with VHL using the following criteria:

      -- Identification of a heterozygous germline pathogenic variant in VHL by molecular genetic testing.


      -- Clinical criteria

    2. Subjects with at least 1 pancreatic manifestation of VHL as documented on any non-invasive imaging study. These manifestations may include:

      • Pancreatic cyst(s)
      • Solid lesions suspicious for microcystic adenoma(s)
      • Solid enhancing lesions suspicious for PNET(s)
      • Any other solid lesion(s) of the pancreas
    3. Age greater than or equal to 12 years.
    4. Ability of subject to understand and the willingness to sign a written informed consent document.


1. Inability of subject to undergo serial non-invasive imaging.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04074135

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Contact: Kristine J Villaruel (240) 858-7033
Contact: Naris Nilubol, M.D. (240) 760-6154

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Naris Nilubol, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT04074135    
Other Study ID Numbers: 190135
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: May 21, 2024
Last Verified: May 16, 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Pancreatic tumors
68-Gallium DOTATATE
MEN1 syndrome
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Adenoma, Islet Cell
Von Hippel-Lindau Disease
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Neurocutaneous Syndromes
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn