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

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

Background:

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.

Objective:

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.

Eligibility:

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

Design:

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.

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Tumors; Von Hippel-Lindau Disease; VHL Pancreatic Neuroendocrine Tumors
• Intervention / Treatment: Drug: 68-Gallium DOTATATE

Detailed Description

Background:

• 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.

Objective:

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

Eligibility:

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

Design:

• 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.

• Study Type: Interventional
• Enrollment (Estimated): 740
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Naris Nilubol, M.D.; Phone Number: (240) 760-6154; Email: niluboln@mail.nih.gov
• Study Contact Backup: Name: Kristine J Villaruel; Phone Number: (240) 858-7033; Email: villaruelkf@mail.nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office; Phone Number: 888-624-1937

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITIERIA:

  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.

     or

     -- 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.

EXCLUSION CRITERIA:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the natural and clinical histories of VHL pancreatic neuroendocrine tumors and cystic lesions	Characterization of the natural and clinical histories of VHL pancreatic neuroendocrine tumors and cystic lesions	15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
predictive value of 68-Gallium DOTATATE PET/CT imaging in patient population	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	at each scheduled visit
growth rate in solid pancreatic tumors	graded tumor biopsy	at each scheduled visit
distribution of time from initial presentation with pancreatic tumors to the time that surgery is recommended	median amount of time from initial presentation with pancreatic tumors to the time that surgery is recommended	at each scheduled visit, until surgery is recommended

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Naris Nilubol, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Estimated): January 30, 2036
• Study Completion (Estimated): July 1, 2036

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 29, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 11, 2024

More Information

Terms related to this study

• Keywords: PNET; Pancreatic tumors; 68-Gallium DOTATATE; MEN1 syndrome; NETest
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Congenital Abnormalities; Digestive System Neoplasms; Endocrine Gland Neoplasms; Genetic Diseases, Inborn; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Pancreatic Diseases; Abnormalities, Multiple; Adenoma; Neurocutaneous Syndromes; Ciliopathies; Angiomatosis; Pancreatic Neoplasms; Neoplasms; Neuroendocrine Tumors; Von Hippel-Lindau Disease; Adenoma, Islet Cell
• Other Study ID Numbers: 190135; 19-C-0135

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No