Kidney CancerNCT00001238
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders
An observational study of Kidney Cancer and Urologic Malignant Disorders, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
We will investigate the clinical manifestations and molecular genetic defects of heritable urologic malignant disorders. Families with urologic malignancy with known or suspected genetic basis will be enrolled. Read more about this study
- Who is it for?
- Ages 2 years and olderHealthy volunteers can take part
- Conditions the study is for
- Kidney Cancer, Urologic Malignant Disorders, Renal Cell Carcinoma
- How many people
- 5,000 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 1990to not given
- Phase
- Observational
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 2 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Individuals with known or suspected inherited urologic malignant disorders and their biologic family members with inherited urologic malignancies will be recruited primarily from the urology, oncology, and genetics communities worldwide
Who may be able to join
- Participants must be greater than or equal to 2 years of age. All participants and guardians (for children younger than 18 years of age) must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed.
- Criteria for Acceptance into this Study (i.e., Disease Categories):
- Disease Category I
- Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is known, including von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).
- Disease Category II
- Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube.
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- Disease Category III
- Individuals and biologic family members who have urologic malignant diseases of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers. A total of 5000 individuals will be enrolled during the study (i.e., that includes individuals registered since the beginning of the protocols in 1989 (89C0086) and 1999 (99C0101)).
- Enrollment per Subject Category (to include both affected and unaffected biologic relatives)
- Subject Category A:
- Category A will include individuals, and biologic relatives, who may or may not be affected who will be evaluated in the Warren G. Magnuson Clinical Center. Individuals in this category will be eligible if they or their biologic family members manifest one or more of the following features in a pattern suggestive of a heritable urologic malignant disorder:
- One or more histologically proven or suspected renal carcinomas and/or cysts
- Cerebellar, spinal, medullary or cerebral hemangioblastomas
- Retinal angioma
- Pancreatic neuro-endocrine carcinoma,micro cystadenoma and/or cysts
- Pheochromocytoma
- Papillary cystadenoma of the epididymis or broad ligament
- Endolymphatic sac tumor
- Cutaneous fibrofolliculomas or multiple skin-colored papules
- History of spontaneous pneumothorax
- Lung cysts
- Thyroid carcinoma
- Intestinal polyposis plus/minus colon cancer
- Cutaneous or Uterine leiomyoma or uterine leiomyosarcoma, sarcoma
- Subject Category B:
- Category B will include individuals and the biologic relatives of patients with inherited urologic malignancies with the above listed clinical findings who live at a distance and who will not be evaluated at the Clinical Center. In some cases, local diagnostic testing may be necessary for these individuals in addition to collection of a blood sample for molecular analysis.
- Subject Category C:
- Category C will include biologic relatives who enroll in this study primarily for genetic linkage studies. These individuals will contribute a blood sample for DNA analysis only. No imaging diagnostic testing will be performed on individuals from this category.
Who cannot join
- None
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
About this study
We will investigate the clinical manifestations and molecular genetic defects of heritable urologic malignant disorders. Families with urologic malignancy with known or suspected genetic basis will be enrolled. Affected individuals or individuals suspected of having a germline urologic malignant disorder will undergo periodic clinical assessment and genetic analyses for the purpose of: 1) definition and characterization of phenotype, 2) determination of the natural history of the disorder, and 3) genotype/phenotype correlation. Genetic linkage studies may be performed in situations in which the genetic basis of the disorder has not been elucidated.
Read the detailed description
Background:
- Disorders under investigation are: Autosomal dominant inherited urologic malignant disorders including: von Hippel-Lindau (VHL), hereditary papillary renal cancer (HPRC), Birt Hogg Dube (BHD) and hereditary leiomyomatosis and renal cell carcinoma (HLRCC) as well as familial renal cancer.
- Studies have led to the identification and characterization of the VHL, HPRC, FLCN and HLRCC genes.
- The genetic etiology of the most common type of inherited kidney cancer, familial renal cancer (FRC), remains to be determined.
Objectives:
- To characterize the natural and clinical histories of inherited urologic malignant disorders.
- To determine the genetic etiology of hereditary urologic malignant disorders in which the gene variation is unknown, by linkage analysis, positional cloning and evaluation of candidate genes.
- To correlate specific mutations and their associated protein domains with disease phenotypic expression based on parameters including presenting age, clinical manifestations, histopathology and rate of recurrence.
- To identify and describe as yet unknown or uncharacterized inherited urologic malignant disorders.
Eligibility:
- Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is known, including von Hippel-Lindau (VHL) and hereditary papillary renal carcinoma (HPRC).
- Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known, specifically hereditary forms of Type II papillary renal cancer, clear cell renal carcinoma, renal oncocytoma, chromophobe renal carcinoma or Birt Hogg Dube.
- Individuals and biologic family members who have urologic malignant diseases of suspected, but not proven genetic etiology, including families with more than one individual affected by the same or related cancers.
Design:
- These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
- Genetic testing will be offered to gain appreciation of the effect of mutations on the relative activity of various germline and somatic mutations.
- We will determine if there is a relationship between mutation and disease manifestations and phenotype.
- Conditions
- Kidney Cancer, Urologic Malignant Disorders, Renal Cell Carcinoma, Familial Renal Cancer (FRC), Clear Cell Renal Cancer
- Keywords
- Hereditary Papillary Renal Cancer (HPRC), Birt Hogg Dube (BHD), Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC), Pheochromocytoma, Von Hippel-Lindau (VHL)
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell, Hereditary leiomyomatosis and renal cell cancer, Pheochromocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Disease Category I | Individuals, biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is known, including VHL and HPRC | |
| Disease Category II | Individuals and biologic family members with a suspected or an established diagnosis of an inherited urologic malignancy in which the disease gene is not yet known | |
| Disease Category III | Individuals and biologic family members with a urologic malignant disease of suspected, but not proven genetic etiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify and describe as yet unknown or uncharacterized inherited urologic malignant disorders.
Collection of blood, tissue \& urine to address further scientific questions related to this protocol.
Measured: on-going
Determine the genetic etiology of hereditary urologic malignant disorders in which the gene variation is unknown, by linkage analysis, positional cloning and evaluation of candidate genes.
Collection of blood, tissue \& urine to address further scientific questions related to this protocol.
Measured: on-going
Correlate specific mutations and their associated protein domains with disease phenotypic expression based on parameters including presenting age, clinical manifestations, histopathology and rate of recurrence.
Collection of blood, tissue \& urine to address further scientific questions related to this protocol.
Measured: on-going
Characterize the natural and clinical histories of inherited urologic malignant disorders.
Collection of blood, tissue \& urine to address further scientific questions related to this protocol.
Measured: on-going
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start5 Dec 1990
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney CancerStudies 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
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- W. Marston Linehan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001238
- Sponsor's protocol ID
- 890086
- Other IDs
- 89-C-0086
- Status last verified
- 13 Oct 2026
- First submitted
- 3 Nov 1999
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.