Von Hippel-Lindau DiseaseNCT00062166
Natural History and Management of Pancreatic Lesions in Von Hippel-Lindau Disease
An observational study of Von Hippel-Lindau Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. These tumors are more aggressive in some people than in others. Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Von Hippel-Lindau Disease
- How many people
- 340 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Apr 2003to 29 Nov 2017
- Phase
- Observational
- 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 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with Von Hippel-Lindau (VHL) disease. Von Hippel-Lindau (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. Other tumors include kidney cancers, pheochromocytoma, eye and central nervous system tumors. These tumors occur at a higher frequency rate than normal population.
Who may be able to join
- Patients who have been diagnosed with Von Hippel Lindau (VHL) using the following criteria: either germ line analysis (12) or clinical criteria and a family history (8, 12) and who have at least 1 pancreatic manifestation of VHL as documented on any non-invasive imaging study. These manifestations include:
- Pancreatic cyst(s).
- Solid lesions suspicious for microcystic adenoma(s).
- Solid enhancing lesions suspicious for primitive neuroectodermal tumor (PNET)(s).
- Any other solid lesion(s) of the pancreas.
- Age greater than or equal to 12 years of age.
- Patients must be willing to return to National Institutes of Health (NIH) for follow-up.
- Patients/parent must be able to sign an informed consent.
Who cannot join
- Patients unwilling to undergo serial non-invasive imaging.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of the Natural History and Management of Pancreatic Lesions Associated With Von Hippel-Lindau
Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. These tumors are more aggressive in some people than in others. To learn more about this disease, its genetic cause and how best to treat it, this study will 1) identify patients with VHL who have pancreatic lesions; 2) examine the characteristics of the lesions and how fast they grow; 3) study how well imaging tests can reveal lesion characteristics that will help in diagnosis; and 4) perform genetic studies using blood and, when possible, tissue samples.
Patients 12 years of age and older with VHL involving the pancreas may be eligible for this study. Participants will undergo some or all of the following tests and procedures:
Read more
- Interviews with a cancer doctor, cancer nurses, and a surgeon (if surgery is recommended).
- Computed tomography (CT) scan of the abdomen, chest, or pelvis. This test uses x-rays to produce images of body tissues and organs in small sections.
- Magnetic resonance imaging (MRI) of the abdomen. This test uses radio waves and a strong magnetic field to produce images of body tissues and organs.
- Ultrasound of the abdomen. This test uses sound waves to create images body tissues and organs.
- Blood tests for routine laboratory chemistries, for tests specific to the pancreas, and for genetic studies
- 24-hour urine studies
After the tests are completed, the doctor will discuss the results with the patient. Patients with a pancreatic tumor that requires surgery will be offered the option of an operation to remove as much tumor as possible. Patients with lesions that are not appropriate for surgery will be asked to return to National Institutes of Health (NIH) for scans and x-rays every year to monitor growth of the lesions. If surgery should become advisable in the future, the option will be discussed at that time. Patients with pancreatic cysts will be asked to return to NIH every 2 years for scans and x-rays to monitor their condition.
Read the detailed description
Background:
Patients with the familial cancer syndrome von Hippel-Lindau (VHL) demonstrate manifestations in a variety of organs among them 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 spread. 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 and germ line and tissue genetic analysis.
Objectives:
To identify patients with VHL having pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas.
To follow patients with VHL and pancreatic manifestations by serial examination with non-invasive imaging studies.
For patients with solid lesions of the pancreas, to determine the rate of growth and to correlate the growth rate with clinical measures of disease progression.
To validate non-invasive imaging methods for differentiating benign solid lesions from lesions with malignant potential.
To characterize the time from initial presentation with pancreatic tumors to the time that surgery is recommended.
Eligibility:
Patients greater than or equal to 12 years of age who have been diagnosed with VHL.
Patients/parent must be able to sign an informed consent and be willing to return to National Institutes of Health (NIH) for follow-up.
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 Urologic Oncology Branch personnel as indicated to rule out or manage other manifestations of VHL. Imaging studies of regions other than the chest and abdomen will be dictated by best clinical practice for the workup and management of VHL manifestations as has been previously published.
All patients enrolled on this study will be offered genetic counseling by a trained genetic counselor.
After their initial on-study evaluation, patients who are not found to have solid lesions of the pancreas but rather have only cystic disease of the pancreas, will be re-screened every two years with non-invasive imaging studies.
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 25 patients per year for a total of 15 years. Thus, we anticipate accruing 600 patients on this protocol.
- Conditions
- Von Hippel-Lindau Disease
- Keywords
- Imaging Studies, Rate of Tumor Growth, Familial Cancer Syndrome, Surgical Resection
- Medical subject headings
- von Hippel-Lindau Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Pancreatic Lesions Defined by Simple Cysts, Microcystic Adenomas, Neuroendocrine Tumors & Other Solid Lesions of the Pancreas Who Had Significant Growth in Lesions or Symptoms Related to the Lesions Requiring Surgical Intervention
Pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas were evaluated by 18F Fludeoxyglucose (18F-FDG-PET) imaging to determine if the participant developed metastatic disease (e.g. tumor spreads to different organs).
Measured: 8 years
Secondary outcomes (4)
Percentage of Participants With Exon 3 Mutation Compared to Participants With Exon 1 or 2 Von Hippel Lindau (VHL) Mutations Who Required an Intervention
Percentage of patients by the location of germline VHL mutations.
Measured: 8 years
Number of Participants From Which We Obtained Tissue From Pancreatic Lesions and Normal Tissue for Genetic Analysis
Count of participants from which we obtained tissue from pancreatic tumor and normal tissue (when applicable) for Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins extraction.
Measured: initiation of study therapy until 2009, approximately 6 years
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: 8 years
Number of Participants With Missense or Non-missense Mutations
Count of participants by the type of Von Hippel-Lindau (VHL) gene mutations.
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2003 (estimated)
- Study start11 Apr 2003
- Primary completion29 Nov 2017
- Study completion29 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Von Hippel-Lindau DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Naris Nilubol, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Naris Nilubol, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00062166
- Sponsor's protocol ID
- 030145
- Other IDs
- 03-C-0145
- Status last verified
- Oct 2018
- First submitted
- 5 Jun 2003
- Last updated
- 14 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Clifford SC, Maher ER. Von Hippel-Lindau disease: clinical and molecular perspectives. Adv Cancer Res. 2001;82:85-105. doi: 10.1016/s0065-230x(01)82003-0.
PubMed 11447766Glenn GM, Daniel LN, Choyke P, Linehan WM, Oldfield E, Gorin MB, Hosoe S, Latif F, Weiss G, Walther M, et al. Von Hippel-Lindau (VHL) disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet. 1991 Jun;87(2):207-10. doi: 10.1007/BF00204184.
PubMed 2066108Gnarra JR, Duan DR, Weng Y, Humphrey JS, Chen DY, Lee S, Pause A, Dudley CF, Latif F, Kuzmin I, Schmidt L, Duh FM, Stackhouse T, Chen F, Kishida T, Wei MH, Lerman MI, Zbar B, Klausner RD, Linehan WM. Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma. Biochim Biophys Acta. 1996 Mar 18;1242(3):201-10. doi: 10.1016/0304-419x(95)00012-5. No abstract available.
PubMed 8603073
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Natural History and Management of Pancreatic Lesions Associated With Von Hippel-Lindau
- ClinicalTrials.gov ID
- NCT00062166
- Acronym / sponsor ID
- 030145
- Conditions
- Von Hippel-Lindau Disease
- Keywords
- Imaging Studies, Rate of Tumor Growth, Familial Cancer Syndrome, Surgical Resection
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 11 Apr 2003 (actual)
- Primary completion
- 29 Nov 2017 (actual)
- Study completion
- 29 Nov 2017 (actual)
- First posted
- 6 Jun 2003 (estimated)
- Results
- Posted 14 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Von Hippel-Lindau disease (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. These tumors are more aggressive in some people than in others. To learn more about this disease, its genetic cause and how best to treat it, this study will 1) identify patients with VHL who have pancreatic lesions; 2) examine the characteristics of the lesions and how fast they grow; 3) study how well imaging tests can reveal lesion characteristics that will help in diagnosis; and 4) perform genetic studies using blood and, when possible, tissue samples.
Patients 12 years of age and older with VHL involving the pancreas may be eligible for this study. Participants will undergo some or all of the following tests and procedures:
- Interviews with a cancer doctor, cancer nurses, and a surgeon (if surgery is recommended).
- Computed tomography (CT) scan of the abdomen, chest, or pelvis. This test uses x-rays to produce images of body tissues and organs in small sections.
- Magnetic resonance imaging (MRI) of the abdomen. This test uses radio waves and a strong magnetic field to produce images of body tissues and organs.
- Ultrasound of the abdomen. This test uses sound waves to create images body tissues and organs.
- Blood tests for routine laboratory chemistries, for tests specific to the pancreas, and for genetic studies
- 24-hour urine studies
After the tests are completed, the doctor will discuss the results with the patient. Patients with a pancreatic tumor that requires surgery will be offered the option of an operation to remove as much tumor as possible. Patients with lesions that are not appropriate for surgery will be asked to return to National Institutes of Health (NIH) for scans and x-rays every year to monitor growth of the lesions. If surgery should become advisable in the future, the option will be discussed at that time. Patients with pancreatic cysts will be asked to return to NIH every 2 years for scans and x-rays to monitor their condition.
Detailed description
Background:
Patients with the familial cancer syndrome von Hippel-Lindau (VHL) demonstrate manifestations in a variety of organs among them 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 spread. 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 and germ line and tissue genetic analysis.
Objectives:
To identify patients with VHL having pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas.
To follow patients with VHL and pancreatic manifestations by serial examination with non-invasive imaging studies.
For patients with solid lesions of the pancreas, to determine the rate of growth and to correlate the growth rate with clinical measures of disease progression.
To validate non-invasive imaging methods for differentiating benign solid lesions from lesions with malignant potential.
To characterize the time from initial presentation with pancreatic tumors to the time that surgery is recommended.
Eligibility:
Patients greater than or equal to 12 years of age who have been diagnosed with VHL.
Patients/parent must be able to sign an informed consent and be willing to return to National Institutes of Health (NIH) for follow-up.
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 Urologic Oncology Branch personnel as indicated to rule out or manage other manifestations of VHL. Imaging studies of regions other than the chest and abdomen will be dictated by best clinical practice for the workup and management of VHL manifestations as has been previously published.
All patients enrolled on this study will be offered genetic counseling by a trained genetic counselor.
After their initial on-study evaluation, patients who are not found to have solid lesions of the pancreas but rather have only cystic disease of the pancreas, will be re-screened every two years with non-invasive imaging studies.
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 25 patients per year for a total of 15 years. Thus, we anticipate accruing 600 patients on this protocol.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with Von Hippel-Lindau (VHL) disease. Von Hippel-Lindau (VHL) is an inherited cancer syndrome. Patients are at risk for developing pancreatic cysts and tumors. Other tumors include kidney cancers, pheochromocytoma, eye and central nervous system tumors. These tumors occur at a higher frequency rate than normal population.
Key inclusion criteria (8 listed)
- Patients who have been diagnosed with Von Hippel Lindau (VHL) using the following criteria: either germ line analysis (12) or clinical criteria and a family history (8, 12) and who have at least 1 pancreatic manifestation of VHL as documented on any non-invasive imaging study. These manifestations include:
- Pancreatic cyst(s).
- Solid lesions suspicious for microcystic adenoma(s).
- Solid enhancing lesions suspicious for primitive neuroectodermal tumor (PNET)(s).
- Any other solid lesion(s) of the pancreas.
Key exclusion criteria (1 listed)
- Patients unwilling to undergo serial non-invasive imaging.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of Patients With Pancreatic Lesions Defined by Simple Cysts, Microcystic Adenomas, Neuroendocrine Tumors & Other Solid Lesions of the Pancreas Who Had Significant Growth in Lesions or Symptoms Related to the Lesions Requiring Surgical Intervention
Time frame: 8 years
Pancreatic lesions defined by simple cysts, microcystic adenomas, neuroendocrine tumors and other solid lesions of the pancreas were evaluated by 18F Fludeoxyglucose (18F-FDG-PET) imaging to determine if the participant developed metastatic disease (e.g. tumor spreads to different organs).
4 secondary outcomes
Percentage of Participants With Exon 3 Mutation Compared to Participants With Exon 1 or 2 Von Hippel Lindau (VHL) Mutations Who Required an Intervention
Time frame: 8 years
Number of Participants From Which We Obtained Tissue From Pancreatic Lesions and Normal Tissue for Genetic Analysis
Time frame: initiation of study therapy until 2009, approximately 6 years
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Time frame: 8 years
Number of Participants With Missense or Non-missense Mutations
Time frame: 8 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11447766Clifford SC, Maher ER. Von Hippel-Lindau disease: clinical and molecular perspectives. Adv Cancer Res. 2001;82:85-105. doi: 10.1016/s0065-230x(01)82003-0.
- Background: PubMed 2066108Glenn GM, Daniel LN, Choyke P, Linehan WM, Oldfield E, Gorin MB, Hosoe S, Latif F, Weiss G, Walther M, et al. Von Hippel-Lindau (VHL) disease: distinct phenotypes suggest more than one mutant allele at the VHL locus. Hum Genet. 1991 Jun;87(2):207-10. doi: 10.1007/BF00204184.
- Background: PubMed 8603073Gnarra JR, Duan DR, Weng Y, Humphrey JS, Chen DY, Lee S, Pause A, Dudley CF, Latif F, Kuzmin I, Schmidt L, Duh FM, Stackhouse T, Chen F, Kishida T, Wei MH, Lerman MI, Zbar B, Klausner RD, Linehan WM. Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma. Biochim Biophys Acta. 1996 Mar 18;1242(3):201-10. doi: 10.1016/0304-419x(95)00012-5. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naris Nilubol, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Von Hippel-Lindau Disease, 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 1 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 14 Nov 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Nov 2018). 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 Patients With Pancreatic Lesions Defined by Simple Cysts, Microcystic Adenomas, Neuroendocrine Tumors & Other Solid Lesions of the Pancreas Who Had Significant Growth in Lesions or Symptoms Related to the Lesions Requiring Surgical Intervention (time frame: 8 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 NCT00062166, 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 14 Nov 2018.