Hereditary Leiomyomatosis Renal Cell Cancer - Study of the Genetic Cause and the Predisposition to Renal Cancer

Kidney Cancer Clinical Trial

Official title:

Hereditary Leiomyomatosis Renal Cell Cancer (HLRCC): Identification of the Disease Gene, and Characterization of the Predisposition to Renal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00050752
• Other study ID #: 030066
• Secondary ID: 03-C-0066
• Status: Recruiting
• Start date: February 24, 2003

Study information

• Verified date: June 3, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Deborah A Nielsen, R.N.
• Phone: (240) 760-6247
• Email: deborah.nielsen[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will investigate what causes hereditary leiomyomatosis renal (kidney) cell cancer, or HLRCC, and how the disease is related to the development of kidney tumors. Leiomyomas are benign (non-cancerous) tumors arising from smooth muscle. HLRCC can cause various health problems. Some people develop red bumps on their skin that can be painful at times. Some women with HLRCC can develop leiomyomas of the uterus. In some families, people with HLRCC develop kidney tumors. This study will try to determine:

• What gene changes (mutations) cause HLRCC

• What kind of kidney tumors develop in HLRCC and how they grow

• What the chance is that a person with HLRCC will develop a kidney tumor

People with known or suspected HLRCC (and their family members of any age) may be eligible for this study. This includes people in families in which one or more members has skin leiomyoma and kidney cancer; skin leiomyoma and uterine leiomyoma; multiple skin leiomyomas; kidney cancer and uterine leiomyomas, or kidney cancer consistent with HLRCC, including, but not limited to, collecting duct or papillary, type II. Candidates will be screened with a physical examination, family history, and, for affected family members, a review of medical records, including pathology slides and computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Participants will undergo tests and procedures that may include the following:

• Review of medical records, x-rays, and tissue slides

• Physical examination and family history

• Skin examination

• Gynecological examination for women

• Interviews with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor

• Blood tests for:

1. Genetic research to identify the gene responsible for HLRCC

2. Evaluation of liver, kidney, heart, pancreas, and thyroid function

3. Complete blood count and clotting profile

4. Pregnancy test for pre-menopausal women

5. PSA test for prostate cancer in men over age 40

• CT or MRI scans (for participants 15 years of age and older only)

• Skin biopsy (surgical removal of a small sample of skin tissue)

• Cheek swab or mouth rinse to collect cells for genetic analysis

• Medical photographs of lesions

• Questionnaire

When the tests are completed, participants will discuss the results with a doctor and possibly a genetic nurse or genetic counselor. The genetic findings will not be revealed to participants because their meaning and implications may not yet be understood. Participants may be asked to return to NIH from every 3 months to every 3 years, depending on their condition, for follow-up examinations and tests.

Description:

Background:

• Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare autosomal dominantly inherited disorder which confers susceptibility to develop cutaneous and uterine leiomyomas and renal cell carcinoma.

• HLRCC is caused by mutations in the Krebs cycle enzyme, fumarate hydratase localized on chromosome 1q42.3-q43.

Objectives:

• Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome

• Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.

• Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.

• Determine genotype/phenotype correlations.

• Determine if other genes caused HLRCC.

Eligibility:

-An individual from a family in which one or more biological family members have:

• Cutaneous leiomyoma and kidney cancer.

• Cutaneous leiomyoma and uterine leiomyoma.

• Multiple cutaneous leiomyoma.

• Kidney cancer and uterine leiomyomata.

• Renal tumor histology consistent with HLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II.

Design:

• These rare biological 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 phenotype.

Other known NCT identifiers

• NCT00055627

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 950
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years and older

Eligibility

• INCLUSION CRITERIA:

Patients suspected or known to have phenotype or genotype suggestive of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (HLRCC), such as:

• Cutaneous leiomyoma and kidney cancer

• Cutaneous leiomyoma and uterine leiomyoma

• Multiple cutaneous leiomyoma

• Kidney cancer and uterine leiomyomata

• Renal tumor histology consistent with HRLRCC including, but not limited to: Collecting Duct and/or Papillary, Type II

• All patients and parents/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. Patients under the age of 18 but who are age 13 or older will be asked to sign an assent document prior to participation.

• Participants must be >= 2 years of age.

• A relative (related by blood) of a patient with a confirmed or suspected diagnosis of HLRCC.

EXCLUSION CRITERIA:

None

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Cutaneous Leiomyoma
• Disease Susceptibility
• Kidney Cancer
• Kidney Neoplasms
• Leiomyoma
• Leiomyomatosis
• Renal Tumor Histology

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574. — View Citation

Linehan WM, Lerman MI, Zbar B. Identification of the von Hippel-Lindau (VHL) gene. Its role in renal cancer. JAMA. 1995 Feb 15;273(7):564-70. No abstract available. — View Citation

Zbar B, Tory K, Merino M, Schmidt L, Glenn G, Choyke P, Walther MM, Lerman M, Linehan WM. Hereditary papillary renal cell carcinoma. J Urol. 1994 Mar;151(3):561-6. doi: 10.1016/s0022-5347(17)35015-2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the incidence and characteristics of HLRCC-associated fumarate hydratase gene mutations.	Molecular genetic differences between normal and tumorigenic fumarate hydratase (fumerase) mutations.	on-going
Primary	Determine the clinical manifestations of HLRCC	Collection of blood, urine and/or benign and malignant tissue.	on-going
Primary	Determine if other genes cause HLRCC.	Molecular genetic differences between normal and tumorigenic cells.	on-going
Primary	Determine genotype/phenotype correlations.	Detection and expression analysis of gene(s).	on-going
Primary	Define the types and characteristics (including patterns of growth) of renal cancer associated with HLRCC.	Detection and expression analysis of gene(s).	on-going
Primary	Define the risk of developing renal cancer, cutaneous leiomyoma and uterine leiomyoma in this hereditary cancer syndrome.	Collection of blood, urine and/or benign and malignant tissue.	on-going

External Links

•   NIH Clinical Center Detailed Web Page