Testicular CancerNCT00342537
Genetics of Familial Testicular Cancer
An observational study of Testicular Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study is a collaboration between the Clinical Genetics Branch of the National Cancer Institute and the International Testicular Cancer Linkage Consortium (ITCLC). The primary goal of the ITCLC is mapping and cloning susceptibility genes for familial TGCT. Read more about this study
- Who is it for?
- Ages 4 to 100 years, men only
- Conditions the study is for
- Testicular Cancer
- How many people
- 1,842 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jan 2004to 14 Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 4 to 100 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Families with at least two histopathologically confirmed cases of TGCT, or a combination of TGCT and extragonadal germ cell tumor, and with DNA from at least one affected case will be enrolled at the U.S., U.K., and Norwegian study sites. For the sub-studies, data will be obtained on all family members (siblings, parents, offspring, aunts, uncles, grandparents, cousins) at up to 3 degrees of genetic relatedness to the proband.
Who may be able to join
- The criterion establishing familial TGCT is the presence of at least two cases of documented GCT in blood relatives.
- A case will be determined to have TGCT according to the following criteria:
- Pathologic confirmation of a germ cell-derived tumor arising in the testis. Estragonadal sperm cell tumors will also be included.
- Germ cell-derived histologies including: seminoma, embryonal carcinoma, endodermal sinus (yolk sac) tumor, gonadoblastoma, choriocarcinoma, teratoma, and mixed germ cell tumor.
- A case will be determined to have TIN on the basis of pathologic confirmation of intratubular malignant germ cells (ITMGCs) as defined by Burke and Mostofi.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors
This study is a collaboration between the Clinical Genetics Branch of the National Cancer Institute and the International Testicular Cancer Linkage Consortium (ITCLC). The primary goal of the ITCLC is mapping and cloning susceptibility genes for familial TGCT. The objectives of the current study are to:
- Identify the genes responsible for testicular germ cell tumor (TGCT) (testicular cancer) in families with an inherited tendency to develop the disease
- Determine if the genes which predispose to developing testicular cancer also increase the risk of other specific types of cancer among first- and second-degree relatives of patients with TGCT
- Determine if the microscopic appearance of familial testicular cancers is different from that of non-familial TGCT
Read more
Patients and family members recruited by the ITCLC in the United Kingdom, the Netherlands, and Norway are eligible for this study. Individuals with the following medical criteria may participate:
- Patients with testicular germ cell cancer who have at least one other blood relative with the disease
- Family members of patients (first- and second-degree relatives)
Participants undergo the following procedures:
- Fill out questionnaires for providing information about a history of cancer in all blood relatives, including parents, siblings, children, grandparents, aunts, uncles, and cousins, and a history of undescended testes in male blood relatives. Participants may be asked permission to contact family members to request their help in the study as well.
- Provide a blood sample for genetic testing related to TGCT (except in children under 16 years old).
- Review of medical records and examination of tumor specimen (patients with TGCT only).
- Confirmation of the diagnosis of other types of cancer in these same families (medical records, pathology repots)
- Review of the testicular cancer tissue obtained at the time of surgery from members of multiple case families, and comparison of these findings with a series of TGCT which have developed in men without a family history.
Read the detailed description
Familial clustering of testicular germ cell tumors (TGCT) is well-documented, and a family history of TGCT is associated with an increased risk of this disease. The International Testicular Cancer Linkage Consortium (ITCLC) has assembled 350 multiple case TGCT families in support of a linkage effort that provisionally mapped a susceptibility gene to chromosome Xq27 in a subset of these kindreds. However, familial TGCT is genetically heterogeneous, thus increasing the need for meticulous case definition and classification in ongoing genetic and etiologic studies. The histopathologic classification of TGCT is very complicated; few pathologists have extensive experience reviewing this uncommon tumor. Basing epidemiologic studies upon local pathology reports may result in failure to recognize etiologically critical TGCT subsets of the kind which have been central to suspecting and defining various hereditary cancer syndromes, such as the multiple inherited renal cancer disorders.
Few studies have addressed the risk of cancer among relatives of sporadic TGCT patients. Recent reports suggest a 20% increase in overall cancer risk among first-degree relatives of TGCT patients and site-specific excess cancer risks in male relatives and in the mothers of TGCT patients. These cancer sites constitute diseases for which there is some prior evidence to suggest a genetic relationship to TGCT. Identification of other cancers as part of the familial TGCT disease spectrum would both provide clinically relevant insight into this syndrome, and enhance the statistical power of gene-seeking linkage analysis.
We propose two studies, each targeting the ITCLC set of high-risk TGCT families, none of which come from the US: (a) Centralized Pathology Review of Familial TGCT; and (b) The Occurrence of Cancer Other than Germ Cell Tumors in TGCT Families. Data will be provided by three of the largest ITCLC contributors; each will contact TGCT probands and their relatives and collect the primary data under their familial and non-familial TGCT, and perform the data analysis for both studies. NCI will neither seek nor receive individual identifying information from any participant. Currently, our UK collaborator has completed acquisition of a Federal Wide Assurance (FWA) and local ethical review. Since this group is contributing 70% of the families in these two projects, we now bring that component before the NCI Special Studies IRB. We shall return to the IRB for review of the other two contributors upon completion of their local ethical review process.
- Conditions
- Testicular Cancer
- Keywords
- Pathology, Genetics, Testicular Cancer, Familial, Cancer Epidemiology
- Medical subject headings
- Testicular Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Discovery of new testicular cancer susceptibilitygenes
This outcome is the responsibility of the total ITCLC consortium, and will draw upon the collection of DNA samples from multiplecase TGCT families assembled for the purpose of gene discovery. That activity isseparate from the two substudies being proposed in the current document.
Measured: Duration of Study
Secondary outcomes (1)
Characterization of the familial testicular cancer syndrome phenotype
- We will quantify the risks of cancers (both all sites combined and site-specific risks) other than TGCT in the relatives of multiple-casefamilies. 2. We will perform a central pathology review in which the familial TGCT cases will be compared with age-matched unselected TGCT cases, to determine whether there are unique histologic features which characterize the familial cases.
Measured: Duration of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start2 Jan 2004
- Primary completion31 Dec 2019
- Study completion14 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Testicular 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
- Family based
- Time perspective
- Other
- Enrolment
- 1,842 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mary L McMaster, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00342537
- Sponsor's protocol ID
- 999904076
- Other IDs
- 04-C-N076
- Status last verified
- Jul 2020
- First submitted
- 19 Jun 2006
- Last updated
- 17 Jul 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Mai PL, Friedlander M, Tucker K, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Bonaiti-Pellie C, Heidenreich A, Albers P, Bodrogi I, Geczi L, Olah E, Daly PA, Guilford P, Fossa SD, Heimdal K, Liubchenko L, Tjulandin SA, Stoll H, Weber W, Easton DF, Dudakia D, Huddart R, Stratton MR, Einhorn L, Korde L, Nathanson KL, Bishop DT, Rapley EA, Greene MH. The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urol Oncol. 2010 Sep-Oct;28(5):492-9. doi: 10.1016/j.urolonc.2008.10.004. Epub 2009 Jan 22.
PubMed 19162511Nathanson KL, Kanetsky PA, Hawes R, Vaughn DJ, Letrero R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Oosterhuis JW, Gillis AJ, Looijenga LH, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Rudd M, Huddart R, Crockford GP, Forman D, Oliver DT, Einhorn L, Weber BL, Kramer J, McMaster M, Greene MH, Pike M, Cortessis V, Chen C, Schwartz SM, Bishop DT, Easton DF, Stratton MR, Rapley EA. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet. 2005 Dec;77(6):1034-43. doi: 10.1086/498455. Epub 2005 Oct 24.
PubMed 16380914Crockford GP, Linger R, Hockley S, Dudakia D, Johnson L, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Forman D, Oliver T, Einhorn L, McMaster M, Kramer J, Greene MH, Weber BL, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Hum Mol Genet. 2006 Feb 1;15(3):443-51. doi: 10.1093/hmg/ddi459. Epub 2006 Jan 11.
PubMed 16407372
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors
- ClinicalTrials.gov ID
- NCT00342537
- Acronym / sponsor ID
- 999904076
- Conditions
- Testicular Cancer
- Keywords
- Pathology, Genetics, Testicular Cancer, Familial, Cancer Epidemiology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,842 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 2 Jan 2004 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 14 Jul 2020 (actual)
- First posted
- 21 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a collaboration between the Clinical Genetics Branch of the National Cancer Institute and the International Testicular Cancer Linkage Consortium (ITCLC). The primary goal of the ITCLC is mapping and cloning susceptibility genes for familial TGCT. The objectives of the current study are to:
- Identify the genes responsible for testicular germ cell tumor (TGCT) (testicular cancer) in families with an inherited tendency to develop the disease
- Determine if the genes which predispose to developing testicular cancer also increase the risk of other specific types of cancer among first- and second-degree relatives of patients with TGCT
- Determine if the microscopic appearance of familial testicular cancers is different from that of non-familial TGCT
Patients and family members recruited by the ITCLC in the United Kingdom, the Netherlands, and Norway are eligible for this study. Individuals with the following medical criteria may participate:
- Patients with testicular germ cell cancer who have at least one other blood relative with the disease
- Family members of patients (first- and second-degree relatives)
Participants undergo the following procedures:
- Fill out questionnaires for providing information about a history of cancer in all blood relatives, including parents, siblings, children, grandparents, aunts, uncles, and cousins, and a history of undescended testes in male blood relatives. Participants may be asked permission to contact family members to request their help in the study as well.
- Provide a blood sample for genetic testing related to TGCT (except in children under 16 years old).
- Review of medical records and examination of tumor specimen (patients with TGCT only).
- Confirmation of the diagnosis of other types of cancer in these same families (medical records, pathology repots)
- Review of the testicular cancer tissue obtained at the time of surgery from members of multiple case families, and comparison of these findings with a series of TGCT which have developed in men without a family history.
Detailed description
Familial clustering of testicular germ cell tumors (TGCT) is well-documented, and a family history of TGCT is associated with an increased risk of this disease. The International Testicular Cancer Linkage Consortium (ITCLC) has assembled 350 multiple case TGCT families in support of a linkage effort that provisionally mapped a susceptibility gene to chromosome Xq27 in a subset of these kindreds. However, familial TGCT is genetically heterogeneous, thus increasing the need for meticulous case definition and classification in ongoing genetic and etiologic studies. The histopathologic classification of TGCT is very complicated; few pathologists have extensive experience reviewing this uncommon tumor. Basing epidemiologic studies upon local pathology reports may result in failure to recognize etiologically critical TGCT subsets of the kind which have been central to suspecting and defining various hereditary cancer syndromes, such as the multiple inherited renal cancer disorders.
Few studies have addressed the risk of cancer among relatives of sporadic TGCT patients. Recent reports suggest a 20% increase in overall cancer risk among first-degree relatives of TGCT patients and site-specific excess cancer risks in male relatives and in the mothers of TGCT patients. These cancer sites constitute diseases for which there is some prior evidence to suggest a genetic relationship to TGCT. Identification of other cancers as part of the familial TGCT disease spectrum would both provide clinically relevant insight into this syndrome, and enhance the statistical power of gene-seeking linkage analysis.
We propose two studies, each targeting the ITCLC set of high-risk TGCT families, none of which come from the US: (a) Centralized Pathology Review of Familial TGCT; and (b) The Occurrence of Cancer Other than Germ Cell Tumors in TGCT Families. Data will be provided by three of the largest ITCLC contributors; each will contact TGCT probands and their relatives and collect the primary data under their familial and non-familial TGCT, and perform the data analysis for both studies. NCI will neither seek nor receive individual identifying information from any participant. Currently, our UK collaborator has completed acquisition of a Federal Wide Assurance (FWA) and local ethical review. Since this group is contributing 70% of the families in these two projects, we now bring that component before the NCI Special Studies IRB. We shall return to the IRB for review of the other two contributors upon completion of their local ethical review process.
Study design
- Observational model
- Family based
- Time perspective
- Other
Who may qualify
- Ages
- 4 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Families with at least two histopathologically confirmed cases of TGCT, or a combination of TGCT and extragonadal germ cell tumor, and with DNA from at least one affected case will be enrolled at the U.S., U.K., and Norwegian study sites. For the sub-studies, data will be obtained on all family members (siblings, parents, offspring, aunts, uncles, grandparents, cousins) at up to 3 degrees of genetic relatedness to the proband.
Key inclusion criteria (5 listed)
- The criterion establishing familial TGCT is the presence of at least two cases of documented GCT in blood relatives.
- Pathologic confirmation of a germ cell-derived tumor arising in the testis. Estragonadal sperm cell tumors will also be included.
- Germ cell-derived histologies including: seminoma, embryonal carcinoma, endodermal sinus (yolk sac) tumor, gonadoblastoma, choriocarcinoma, teratoma, and mixed germ cell tumor.
- A case will be determined to have TIN on the basis of pathologic confirmation of intratubular malignant germ cells (ITMGCs) as defined by Burke and Mostofi.
Key exclusion criteria (0 listed)
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
Discovery of new testicular cancer susceptibilitygenes
Time frame: Duration of Study
This outcome is the responsibility of the total ITCLC consortium, and will draw upon the collection of DNA samples from multiplecase TGCT families assembled for the purpose of gene discovery. That activity isseparate from the two substudies being proposed in the current document.
1 secondary outcome
Characterization of the familial testicular cancer syndrome phenotype
Time frame: Duration of Study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
- Background: PubMed 19162511Mai PL, Friedlander M, Tucker K, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Bonaiti-Pellie C, Heidenreich A, Albers P, Bodrogi I, Geczi L, Olah E, Daly PA, Guilford P, Fossa SD, Heimdal K, Liubchenko L, Tjulandin SA, Stoll H, Weber W, Easton DF, Dudakia D, Huddart R, Stratton MR, Einhorn L, Korde L, Nathanson KL, Bishop DT, Rapley EA, Greene MH. The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urol Oncol. 2010 Sep-Oct;28(5):492-9. doi: 10.1016/j.urolonc.2008.10.004. Epub 2009 Jan 22.
- Background: PubMed 16380914Nathanson KL, Kanetsky PA, Hawes R, Vaughn DJ, Letrero R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Oosterhuis JW, Gillis AJ, Looijenga LH, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Rudd M, Huddart R, Crockford GP, Forman D, Oliver DT, Einhorn L, Weber BL, Kramer J, McMaster M, Greene MH, Pike M, Cortessis V, Chen C, Schwartz SM, Bishop DT, Easton DF, Stratton MR, Rapley EA. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet. 2005 Dec;77(6):1034-43. doi: 10.1086/498455. Epub 2005 Oct 24.
- Background: PubMed 16407372Crockford GP, Linger R, Hockley S, Dudakia D, Johnson L, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Forman D, Oliver T, Einhorn L, McMaster M, Kramer J, Greene MH, Weber BL, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Hum Mol Genet. 2006 Feb 1;15(3):443-51. doi: 10.1093/hmg/ddi459. Epub 2006 Jan 11.
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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.
Mary L McMaster, 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 Testicular Cancer, 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 5 inclusion and 0 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 17 Jul 2020. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Discovery of new testicular cancer susceptibilitygenes (time frame: Duration of Study). 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 NCT00342537, 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 17 Jul 2020.