Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors

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Brief Title

Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors

Official Title

Evaluation of the Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors

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


      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.

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


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


      - 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

Study Phase

Phase 2

Study Type


Primary Outcome

Characterization of the natural and clinical histories of VHL pancreatic neuroendocrine tumors and cystic lesions

Secondary Outcome

 predictive value of 68-Gallium DOTATATE PET/CT imaging in patient population


VHL Pancreatic Neuroendocrine Tumors


68-Gallium DOTATATE

Study Arms / Comparison Groups

 1/ Arm 1
Description:  Study natural history of VHL pancreatic neuroendocrine tumors with yearly 68-Gallium DOTATATE PET/CT research scans.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

June 2, 2020

Completion Date

July 1, 2036

Primary Completion Date

January 30, 2036

Eligibility Criteria


               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.




12 Years - N/A

Accepts Healthy Volunteers



Naris Nilubol, M.D., (240) 858-7033, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

Naris Nilubol, M.D., Principal Investigator, National Cancer Institute (NCI)

Verification Date

October 3, 2022