Endometrial HyperplasiaNCT00339651
Preliminary Study of Endometrial Hyperplasia Groundwork for a Study to Define Precursors of Endometrial Cancer
An observational study of Endometrial Hyperplasia and Endometrial Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study, conducted jointly by the National Cancer Institute and the Kaiser Permanente Center for Health Research Northwest (KPCHRN) in Portland, Oregon, will lay the groundwork for a future study to identify precursors of endometrial cancer; that is, conditions that precede development of cancer of the lining of… Read more about this study
- Who is it for?
- Ages 40 to 120 years, women only
- Conditions the study is for
- Endometrial Hyperplasia, Endometrial Cancer, Postmenopausal Bleeding
- How many people
- 745 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Nov 2002to 6 Aug 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 40 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: We are conducting a nested case-control study of adenocarcinoma of the endometrium within a retrospective cohort of one large managed health care organization in the Northwest U.S. Cases, i.e., women who developed endometrial cancer after a diagnosis of endometrial hyperplasia, will be compared with women who were diagnosed with endometrial hyperplasia but did not develop cancer during an equivalent follow-up period, after controlling for relevant confounders.@@@@@@
Who may be able to join
- All women who were members of the KPNW health plan between 1970 and 2003 who were at risk of developing endometrial carcinoma will be eligible.
Who cannot join
- Women will be considered ineligible if they had substantial gaps in KPNW coverage during the years between the index biopsy and diagnosis date (cases) or censoring date (controls).
- NCI and KPNW will review otherwise eligible women who have coverage gaps to identify substantial gaps and determine eligibility on an individual basis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Kaiser Permanente Northwest
Hillsboro, Oregon, 97124
About this study
Official title: Preliminary Study of Endometrial Hyperplasia: Groundwork for a Study to Define an Optimal Classification of Endometrial Carcinoma Precursors
This study, conducted jointly by the National Cancer Institute and the Kaiser Permanente Center for Health Research Northwest (KPCHRN) in Portland, Oregon, will lay the groundwork for a future study to identify precursors of endometrial cancer; that is, conditions that precede development of cancer of the lining of the uterus. The diagnosis of endometrial hyperplasia (a condition of abnormal proliferation of endometrial tissue) includes most precursors of endometrial cancer, as well as many benign conditions. Currently, three methods of classifying endometrial cancer precursors have been suggested based on endometrial hyperplasia findings, but it is not known which classification best predicts cancer risk.
This study will examine surgical specimens of hyperplasia and cancer from women diagnosed with endometrial cancer at least 2 years after a diagnosis of endometrial hyperplasia. Investigators will estimate the percentage of cases with different degrees of hyperplasia, and assess the subsequent cancers that developed. This will allow them to rank hyperplasia lesions according to cancer risk and identify lesions that represent the most immediate cancer precursors. They will also review patients medical charts for information related to cancer risk and treatment.
Study participants will include women enrolled in the KPCHRN who are 40 years of age or older and who were diagnosed with endometrial cancer at least 2 years after being diagnosed with endometrial hyperplasia.
Read the detailed description
Three systems have been proposed to classify endometrial carcinoma precursors, but it is currently unclear which system best predicts cancer risk and is most reproducible. The optimal surrogate endpoint for endometrial carcinoma is therefore unknown. The pathologic diagnosis of endometrial hyperplasia (EH) includes most suspected immediate precursors and many mild, highly reversible proliferations. We propose an exploratory study to assess the feasibility of investigating EH as a source of an endometrial carcinoma surrogate endpoint.
We are conducting a nested case-control study within a large, population-based health care plan. We will identify cases, defined as women who were diagnosed with EH at least one year before being diagnosed with endometrial carcinoma or severe atypical hyperplasia at hysterectomy, through a computerized search of plan databases. We will retrieve the slides from the matching biopsy and hysterectomy on which carcinoma was diagnosed. Women ages 40 or older who were plan members and received a biopsy or curettage diagnosis of EH between 1970 and 2002 will be eligible to be a case.
We will perform an initial histologic review of cases index biopsy slides to assess two types of misclassification known to affect the diagnosis of EH: a) false-negative endometrial carcinoma (i.e., prevalent carcinoma t the time of EH diagnosis) and b) false-positive EH (i.e., a benign, non-hyperplastic lesion). From cases physical records and linked computer records, we will collect data on histopathologic classification of EH lesions and subsequent carcinomas; descriptive data (e.g., patient weight, parity, and menopausal status); and a summary of relevant treatments and follow-up procedures (e.g., hormone therapy or additional clinical procedures).
We will select controls, defined as women who were diagnosed with EH but then did not develop endometrial carcinoma or undergo hysterectomy for a follow-up interval that is equivalent to the follow-up interval of the cases. Controls will be individually matched to cases on age at EH diagnosis, date of EH diagnosis, and duration of follow-up, and also counter-matched based on the original EH diagnosis. After selecting 3 controls per case, we will assemble the same data from controls: histologic review of original slides, descriptive data from medical records databases, and treatment and follow-up procedure data from linked databases.
These data will then be used to estimate the cancer risk associated with specific EH classifications, identify other patient or clinical factors that might modify those risks, explore predictors of EH, and explore molecular factors that might influence the probability of developing carcinoma after a diagnosis of EH.
- Keywords
- Precursors, Endometrial Cancer, Hyperplasia, Progression
- Medical subject headings
- Endometrial Hyperplasia, Endometrial Neoplasms, Uterine Hemorrhage, Hyperplasia, Disease Progression
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 |
|---|---|---|
| Cases | Women in one large U.S. health care plan. Cases will consist of women who developed endometrial carcinoma or censored complex atypical hyperplasia at least 1 year after receiving a diagnosis of endometrial hyperplasia. | |
| Controls | Women in one large U.S. health care plan. Controls will consist of individually matched women who received a diagnosis of endometrial hyperplasia at the same age and date as the cases and were cancer-free and hysterectomy-free until the date at which the index cases were diagnosed with endometrial carcinoma or censored complex atypical hyperplasia. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endometrial cancer and endometrial hyperplasia.
Formalin fixed paraffin embedded tissue blocks and pathology slides from women with endometrial cancer and women with endometrial hyperplasia with covariate data from medical records.
Measured: Cases were diagnosed between 2003 and 2012. Tissue collection is ongoing
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 start25 Nov 2002
- Primary completion6 Aug 2020
- Study completion6 Aug 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 Endometrial HyperplasiaStudies 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
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 745 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nicolas Wentzensen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00339651
- Sponsor's protocol ID
- 999903053
- Other IDs
- 03-C-N053
- Status last verified
- Aug 2020
- First submitted
- 19 Jun 2006
- Last updated
- 14 Aug 2020
- Results posted
- No
Publications
Skov BG, Broholm H, Engel U, Franzmann MB, Nielsen AL, Lauritzen AF, Skov T. Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia. Int J Gynecol Pathol. 1997 Jan;16(1):33-7. doi: 10.1097/00004347-199701000-00006.
PubMed 8986530Bergeron C, Nogales FF, Masseroli M, Abeler V, Duvillard P, Muller-Holzner E, Pickartz H, Wells M. A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens. Am J Surg Pathol. 1999 Sep;23(9):1102-8. doi: 10.1097/00000478-199909000-00014.
PubMed 10478671Baak JP, Orbo A, van Diest PJ, Jiwa M, de Bruin P, Broeckaert M, Snijders W, Boodt PJ, Fons G, Burger C, Verheijen RH, Houben PW, The HS, Kenemans P. Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias. Am J Surg Pathol. 2001 Jul;25(7):930-5. doi: 10.1097/00000478-200107000-00012.
PubMed 11420465
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preliminary Study of Endometrial Hyperplasia: Groundwork for a Study to Define an Optimal Classification of Endometrial Carcinoma Precursors
- ClinicalTrials.gov ID
- NCT00339651
- Acronym / sponsor ID
- 999903053
- Keywords
- Precursors, Endometrial Cancer, Hyperplasia, Progression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 745 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 25 Nov 2002 (actual)
- Primary completion
- 6 Aug 2020 (actual)
- Study completion
- 6 Aug 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, conducted jointly by the National Cancer Institute and the Kaiser Permanente Center for Health Research Northwest (KPCHRN) in Portland, Oregon, will lay the groundwork for a future study to identify precursors of endometrial cancer; that is, conditions that precede development of cancer of the lining of the uterus. The diagnosis of endometrial hyperplasia (a condition of abnormal proliferation of endometrial tissue) includes most precursors of endometrial cancer, as well as many benign conditions. Currently, three methods of classifying endometrial cancer precursors have been suggested based on endometrial hyperplasia findings, but it is not known which classification best predicts cancer risk.
This study will examine surgical specimens of hyperplasia and cancer from women diagnosed with endometrial cancer at least 2 years after a diagnosis of endometrial hyperplasia. Investigators will estimate the percentage of cases with different degrees of hyperplasia, and assess the subsequent cancers that developed. This will allow them to rank hyperplasia lesions according to cancer risk and identify lesions that represent the most immediate cancer precursors. They will also review patients medical charts for information related to cancer risk and treatment.
Study participants will include women enrolled in the KPCHRN who are 40 years of age or older and who were diagnosed with endometrial cancer at least 2 years after being diagnosed with endometrial hyperplasia.
Detailed description
Three systems have been proposed to classify endometrial carcinoma precursors, but it is currently unclear which system best predicts cancer risk and is most reproducible. The optimal surrogate endpoint for endometrial carcinoma is therefore unknown. The pathologic diagnosis of endometrial hyperplasia (EH) includes most suspected immediate precursors and many mild, highly reversible proliferations. We propose an exploratory study to assess the feasibility of investigating EH as a source of an endometrial carcinoma surrogate endpoint.
We are conducting a nested case-control study within a large, population-based health care plan. We will identify cases, defined as women who were diagnosed with EH at least one year before being diagnosed with endometrial carcinoma or severe atypical hyperplasia at hysterectomy, through a computerized search of plan databases. We will retrieve the slides from the matching biopsy and hysterectomy on which carcinoma was diagnosed. Women ages 40 or older who were plan members and received a biopsy or curettage diagnosis of EH between 1970 and 2002 will be eligible to be a case.
We will perform an initial histologic review of cases index biopsy slides to assess two types of misclassification known to affect the diagnosis of EH: a) false-negative endometrial carcinoma (i.e., prevalent carcinoma t the time of EH diagnosis) and b) false-positive EH (i.e., a benign, non-hyperplastic lesion). From cases physical records and linked computer records, we will collect data on histopathologic classification of EH lesions and subsequent carcinomas; descriptive data (e.g., patient weight, parity, and menopausal status); and a summary of relevant treatments and follow-up procedures (e.g., hormone therapy or additional clinical procedures).
We will select controls, defined as women who were diagnosed with EH but then did not develop endometrial carcinoma or undergo hysterectomy for a follow-up interval that is equivalent to the follow-up interval of the cases. Controls will be individually matched to cases on age at EH diagnosis, date of EH diagnosis, and duration of follow-up, and also counter-matched based on the original EH diagnosis. After selecting 3 controls per case, we will assemble the same data from controls: histologic review of original slides, descriptive data from medical records databases, and treatment and follow-up procedure data from linked databases.
These data will then be used to estimate the cancer risk associated with specific EH classifications, identify other patient or clinical factors that might modify those risks, explore predictors of EH, and explore molecular factors that might influence the probability of developing carcinoma after a diagnosis of EH.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | –Women in one large U.S. health care plan. Cases will consist of women who developed endometrial carcinoma or censored complex atypical hyperplasia at least 1 year after receiving a diagnosis of endometrial hyperplasia. |
| Controls | – | –Women in one large U.S. health care plan. Controls will consist of individually matched women who received a diagnosis of endometrial hyperplasia at the same age and date as the cases and were cancer-free and hysterectomy-free until the date at which the index cases were diagnosed with endometrial carcinoma or censored complex atypical hyperplasia. |
Who may qualify
- Ages
- 40 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We are conducting a nested case-control study of adenocarcinoma of the endometrium within a retrospective cohort of one large managed health care organization in the Northwest U.S. Cases, i.e., women who developed endometrial cancer after a diagnosis of endometrial hyperplasia, will be compared with women who were diagnosed with endometrial hyperplasia but did not develop cancer during an equivalent follow-up period, after controlling for relevant confounders.@@@@@@
Key inclusion criteria (1 listed)
- All women who were members of the KPNW health plan between 1970 and 2003 who were at risk of developing endometrial carcinoma will be eligible.
Key exclusion criteria (2 listed)
- Women will be considered ineligible if they had substantial gaps in KPNW coverage during the years between the index biopsy and diagnosis date (cases) or censoring date (controls).
- NCI and KPNW will review otherwise eligible women who have coverage gaps to identify substantial gaps and determine eligibility on an individual basis.
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
Endometrial cancer and endometrial hyperplasia.
Time frame: Cases were diagnosed between 2003 and 2012. Tissue collection is ongoing
Formalin fixed paraffin embedded tissue blocks and pathology slides from women with endometrial cancer and women with endometrial hyperplasia with covariate data from medical records.
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 14 Aug 2020.
- Background: PubMed 8986530Skov BG, Broholm H, Engel U, Franzmann MB, Nielsen AL, Lauritzen AF, Skov T. Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia. Int J Gynecol Pathol. 1997 Jan;16(1):33-7. doi: 10.1097/00004347-199701000-00006.
- Background: PubMed 10478671Bergeron C, Nogales FF, Masseroli M, Abeler V, Duvillard P, Muller-Holzner E, Pickartz H, Wells M. A multicentric European study testing the reproducibility of the WHO classification of endometrial hyperplasia with a proposal of a simplified working classification for biopsy and curettage specimens. Am J Surg Pathol. 1999 Sep;23(9):1102-8. doi: 10.1097/00000478-199909000-00014.
- Background: PubMed 11420465Baak JP, Orbo A, van Diest PJ, Jiwa M, de Bruin P, Broeckaert M, Snijders W, Boodt PJ, Fons G, Burger C, Verheijen RH, Houben PW, The HS, Kenemans P. Prospective multicenter evaluation of the morphometric D-score for prediction of the outcome of endometrial hyperplasias. Am J Surg Pathol. 2001 Jul;25(7):930-5. doi: 10.1097/00000478-200107000-00012.
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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.
Nicolas Wentzensen, 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 Endometrial Hyperplasia and Endometrial 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 1 inclusion and 2 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 Aug 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?
Endometrial cancer and endometrial hyperplasia. (time frame: Cases were diagnosed between 2003 and 2012. Tissue collection is ongoing). 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 NCT00339651, 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 Aug 2020.