Endometrial Neoplasm MalignantNCT03498924
Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue
An observational study of Endometrial Neoplasm Malignant, run by Fundación Investigación Sanitaria en León at 1 site in Spain.
Trial summary
Endometrial cancer is the most common malignant tumor of the female genital tract in our means. The diagnosis is made by endometrial biopsy sampling with anatomopathological analysis which pinpoints the cell line and the level of cell differentiation. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Endometrial Neoplasm Malignant
- What is being tested?
- Measure of biomarkers in serum and endometrial tissue
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- 1 Aug 2017to 1 Jun 2019
- 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 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Every patient who is treated in Hospital de Leon of endometrial disease between August 2017 and the end of the recruitment
Who may be able to join
- Female
- Of legal age (≥ 18 years)
- Wish to participate in the research study and sign consent forms voluntarily
- Patients diagnosed of endometrial cancer derived to hysterectomy
Who cannot join
- Patients that underwent surgery for other malignant pathologies, whether for ovarian carcinoma, cervical carcinoma or uterine sarcoma.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue Samples
Endometrial cancer is the most common malignant tumor of the female genital tract in our means. The diagnosis is made by endometrial biopsy sampling with anatomopathological analysis which pinpoints the cell line and the level of cell differentiation. Its treatment is surgical with adjuvant treatment (chemotherapy or radiotherapy) besides, depending on the staging. Thus far, in the first diagnosis it is only request the tumor marker CA125 in serum, but there are studies that identify the HE4 protein in blood as a feasible marker for endometrial cancer. Furthermore, the staging changes the surgical and the adjuvant treatment: in its early stages, surgery is based on hysterectomy and double adnexectomy, however, in later stages it is necessary to add pelvic and paraaortic lymphadenectomy with the associated comorbidity. This makes extremely important that the preoperative diagnosis is accurate. The aim of this study is to identify and characterize the HE4, Ki67, p53 and other potential biomarkers in endometrial tissue in order to diagnose patients with disease only with a biopsy. Moreover, the investigators are searching for connections among these markers and prognostic factors such as grade of cell differentiation, cell line, lymphatic affectation, tumor stage or even features as survival or disease free survival.
Read the detailed description
List of abbreviations:
- HE4: Human Epididymis Protein 4
- CA125: Carbohydrate Antigen 125
- Ki67: antigen KI67
- EC: Endometrial Cancer
- CT: Computed Tomography
- NMR: Nuclear Magnetic Resonance
- FIGO: International Federation of Gynecology and Obstetrics
The purpose of this study is:
- The proportion of positive H-score of HE4, as quantified in endometrial tissue. It is significantly higher in patients with endometrial cancer than in non-EC patients.
- Percentage of HE4, CA125 and other markers positives in cases and controls.
- Concentration of HE4 in tissue, as measured by H-score, correlates linearly with HE4 concentration in serum, as measured in terms of ppmol/l.
- Differences in serum CA125 levels between cases and controls.
- Quantification of tissue tumor markers of EC patients, per disease stages.
- Relation of the immunohistochemistry intensity with survival and disease-free survival times.
- Analysis of other risk factors adjusting for known variables like age, menopausal status, hypertension, diabetes or obesity.
- Feasibility of the technique.
Steps in the study:
- Patients enter the study when a diagnosis of endometrial cancer is done. As it is ordinary in the clinical practice the diagnosis is made with an endometrial tissue sample taken in the office which is afterwards studied by a pathologist, who makes the final diagnosis.
- Patients undergo the regular preoperative study with pelvic ultrasound, CT and/or NMR for the extension study, blood tests and the preanaesthetic consultation. As it is registered in the protocol of Endometrial Cancer Treatment.
- Then a matched control is selected from the group of patients that are going to be hysterectomized for other non-malignant reasons (abdominal way, vaginal, or laparoscopic way). Variables considered for matching are: age (variability of five years), pre or postmenopausal status, hypertension, obesity and diabetes.
- Every patient then is asked for accept and sign the informed consent. The next step is to prepare the patient for the surgery. In this moment the serum sample is taken. Subsequently the surgery will be performed.
- Then the anatomopathological study is conducted over the preoperative tissue sample. HE4 marker in endometrial tissue is defined by H-Score while Ki67 and p53 are defined as usual. Although Ki67 is matched in > or <25% of expression instead of 14% as it is made in breast cancer tissue samples.
- After discharge, the patient will be follow-up for two years in order to register the evolution of the disease.
- Conditions
- Endometrial Neoplasm Malignant
- Being tested
- Measure of biomarkers in serum and endometrial tissue
- Keywords
- tumor marker, HE4, CA125, staging, diagnosis, Endometrial Cancer
- Medical subject headings
- Endometrial Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Measure of biomarkers in serum and endometrial tissueDiagnostic test
Blood sample and endometrial sample
| Study group | Role | What they receive |
|---|---|---|
| CASES | Patients with endometrial cancer Receives: Diagnostic Test: Measure of biomarkers in serum and endometrial tissue | |
| CONTROLS | Matched controls without neoplasm disease Receives: Diagnostic Test: Measure of biomarkers in serum and endometrial tissue |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of positive H-score of HE4.
HE4 quantified in endometrial tissue is significantly higher in patients with endometrial cancer than in non-EC patients
Measured: Two years
Secondary outcomes (12)
Concentration of HE4 in tissue correlates linearly with HE4 in serum.
Comparison of tissue H-score with ppmol/L in serum
Measured: Two years
Difference in preoperative serum CA125 levels in cases and controls.
Measured in terms of U/mL
Measured: Two years
Difference in preoperative serum HE4 levels in cases and controls.
Measured in terms of ppmol/L
Measured: Two years
Disease stages
FIGO stages: postsurgical classification drawn up to define the extent of spread of genital cancer
Measured: Two years
Tissue tumor marker HE4
H-score determination: Immunohistochemistry results can be evaluated by a semiquantitative approach used to assign an H-score (or "histo" score) to tumor samples. Cytoplasmic staining will be graded for intensity (0-negative, 1-weak, 2-moderate and 3-strong) and the percentage of positive cells was scored as 0 (0%), 1 (1-10%), 2 (11-50%) and 3 (51-100%).
Single scale with scores 0-9 will be obtained by multiplying the intensity and the percentage staining score, and a total score will be calculated by grouping score 0 in total score 0, 1-3 in total score 1, 4-6 in total score 2 and 7-9 in total score 3.
The assumption is that as higher is the score the level of cell differentiation would be minor.
Measured: Two years
Relation of the immunohistochemistry intensity in H-score with overall survival
HE4 biomarker measured with H-score in endometrial tissue, explained in outcome 5, in relation to length of time of survival
Measured: Through study completion, an average of 2 years
Relation of the immunohistochemistry intensity in H-score with disease-free survival
HE4 biomarker measured with H-score in endometrial tissue, explained in outcome 5, in relation to length of time after primary treatment that the patient survives without any signs or symptoms of that cancer.
Measured: Through study completion, an average of 2 years
Analysis of outcomes in relation to age
Age of patients is one of the known risk factors for EC, we are going to analysis the results of the study with this variable. As elder the relative risk is higher though there is no accurate cut-off point.
Measured: Two years
Analysis of outcomes in relation to menopausal status
Menopausal status is determined by questionnaire during the preoperative consultant. It is another risk factor for EC, the postmenopausal status has higher relative risk than premenopausal status.
Measured: Two years
Analysis of outcomes in relation to hypertension
Hypertension is diagnosed previously to surgery as Blood Pressure over 140/90 mm Hg in several measures. There is a known high relative risk of EC in patients diagnosed with hypertension.
Measured: Two years
Analysis of outcomes in relation to diabetes
Diabetes is a disease previously diagnosed by high glucose levels in blood. There is a known high relative risk of EC in patients diagnosed with diabetes.
Measured: Two years
Analysis of outcomes in relation to obesity
Obesity is defined as BMI >27 kg/m2. There is a known high relative risk of EC in patients diagnosed with obesity.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2018
- Study start1 Aug 2017
- Primary completion1 Aug 2018
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Endometrial Neoplasm MalignantStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Investigación Sanitaria en León
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tatiana Cuesta-Guardiola, Fundación Investigación Sanitaria en León
- Investigators
- Tatiana Cuesta-Guardiola, Medicine, Principal investigator, Hospital de Leon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498924
- Sponsor's protocol ID
- STUDY17104
- Status last verified
- Feb 2020
- First submitted
- 23 Feb 2018
- Last updated
- 11 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
PubMed 29313949Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.
PubMed 3652025Li X, Gao Y, Tan M, Zhuang H, Gao J, Hu Z, Wang H, Zhu L, Liu J, Lin B. Expression of HE4 in Endometrial Cancer and Its Clinical Significance. Biomed Res Int. 2015;2015:437468. doi: 10.1155/2015/437468. Epub 2015 Oct 11.
PubMed 26539494Bignotti E, Ragnoli M, Zanotti L, Calza S, Falchetti M, Lonardi S, Bergamelli S, Bandiera E, Tassi RA, Romani C, Todeschini P, Odicino FE, Facchetti F, Pecorelli S, Ravaggi A. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011 Apr 26;104(9):1418-25. doi: 10.1038/bjc.2011.109. Epub 2011 Apr 5.
PubMed 21468050
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Identification and Characterization of Endometrial Cancer With Specific Tumor Markers in Serum and Endometrial Tissue Samples
- ClinicalTrials.gov ID
- NCT03498924
- Acronym / sponsor ID
- STUDY17104
- Conditions
- Endometrial Neoplasm Malignant
- Keywords
- tumor marker, HE4, CA125, staging, diagnosis, Endometrial Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Fundación Investigación Sanitaria en LeónUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Aug 2018 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 17 Apr 2018 (actual)
- 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.
Endometrial cancer is the most common malignant tumor of the female genital tract in our means. The diagnosis is made by endometrial biopsy sampling with anatomopathological analysis which pinpoints the cell line and the level of cell differentiation. Its treatment is surgical with adjuvant treatment (chemotherapy or radiotherapy) besides, depending on the staging. Thus far, in the first diagnosis it is only request the tumor marker CA125 in serum, but there are studies that identify the HE4 protein in blood as a feasible marker for endometrial cancer. Furthermore, the staging changes the surgical and the adjuvant treatment: in its early stages, surgery is based on hysterectomy and double adnexectomy, however, in later stages it is necessary to add pelvic and paraaortic lymphadenectomy with the associated comorbidity. This makes extremely important that the preoperative diagnosis is accurate. The aim of this study is to identify and characterize the HE4, Ki67, p53 and other potential biomarkers in endometrial tissue in order to diagnose patients with disease only with a biopsy. Moreover, the investigators are searching for connections among these markers and prognostic factors such as grade of cell differentiation, cell line, lymphatic affectation, tumor stage or even features as survival or disease free survival.
Detailed description
List of abbreviations:
- HE4: Human Epididymis Protein 4
- CA125: Carbohydrate Antigen 125
- Ki67: antigen KI67
- EC: Endometrial Cancer
- CT: Computed Tomography
- NMR: Nuclear Magnetic Resonance
- FIGO: International Federation of Gynecology and Obstetrics
The purpose of this study is:
- The proportion of positive H-score of HE4, as quantified in endometrial tissue. It is significantly higher in patients with endometrial cancer than in non-EC patients.
- Percentage of HE4, CA125 and other markers positives in cases and controls.
- Concentration of HE4 in tissue, as measured by H-score, correlates linearly with HE4 concentration in serum, as measured in terms of ppmol/l.
- Differences in serum CA125 levels between cases and controls.
- Quantification of tissue tumor markers of EC patients, per disease stages.
- Relation of the immunohistochemistry intensity with survival and disease-free survival times.
- Analysis of other risk factors adjusting for known variables like age, menopausal status, hypertension, diabetes or obesity.
- Feasibility of the technique.
Steps in the study:
- Patients enter the study when a diagnosis of endometrial cancer is done. As it is ordinary in the clinical practice the diagnosis is made with an endometrial tissue sample taken in the office which is afterwards studied by a pathologist, who makes the final diagnosis.
- Patients undergo the regular preoperative study with pelvic ultrasound, CT and/or NMR for the extension study, blood tests and the preanaesthetic consultation. As it is registered in the protocol of Endometrial Cancer Treatment.
- Then a matched control is selected from the group of patients that are going to be hysterectomized for other non-malignant reasons (abdominal way, vaginal, or laparoscopic way). Variables considered for matching are: age (variability of five years), pre or postmenopausal status, hypertension, obesity and diabetes.
- Every patient then is asked for accept and sign the informed consent. The next step is to prepare the patient for the surgery. In this moment the serum sample is taken. Subsequently the surgery will be performed.
- Then the anatomopathological study is conducted over the preoperative tissue sample. HE4 marker in endometrial tissue is defined by H-Score while Ki67 and p53 are defined as usual. Although Ki67 is matched in > or <25% of expression instead of 14% as it is made in breast cancer tissue samples.
- After discharge, the patient will be follow-up for two years in order to register the evolution of the disease.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CASES | – | Diagnostic Test: Measure of biomarkers in serum and endometrial tissuePatients with endometrial cancer |
| CONTROLS | – | Diagnostic Test: Measure of biomarkers in serum and endometrial tissueMatched controls without neoplasm disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Every patient who is treated in Hospital de Leon of endometrial disease between August 2017 and the end of the recruitment
Key inclusion criteria (4 listed)
- Female
- Of legal age (≥ 18 years)
- Wish to participate in the research study and sign consent forms voluntarily
- Patients diagnosed of endometrial cancer derived to hysterectomy
Key exclusion criteria (1 listed)
- Patients that underwent surgery for other malignant pathologies, whether for ovarian carcinoma, cervical carcinoma or uterine sarcoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Measure of biomarkers in serum and endometrial tissueBlood sample and endometrial sample | Diagnostic test | CASES, CONTROLS |
Primary outcome
The proportion of positive H-score of HE4.
Time frame: Two years
HE4 quantified in endometrial tissue is significantly higher in patients with endometrial cancer than in non-EC patients
12 secondary outcomes
Concentration of HE4 in tissue correlates linearly with HE4 in serum.
Time frame: Two years
Difference in preoperative serum CA125 levels in cases and controls.
Time frame: Two years
Difference in preoperative serum HE4 levels in cases and controls.
Time frame: Two years
Disease stages
Time frame: Two years
Tissue tumor marker HE4
Time frame: Two years
Relation of the immunohistochemistry intensity in H-score with overall survival
Time frame: Through study completion, an average of 2 years
Relation of the immunohistochemistry intensity in H-score with disease-free survival
Time frame: Through study completion, an average of 2 years
Analysis of outcomes in relation to age
Time frame: Two years
Analysis of outcomes in relation to menopausal status
Time frame: Two years
Analysis of outcomes in relation to hypertension
Time frame: Two years
Analysis of outcomes in relation to diabetes
Time frame: Two years
Analysis of outcomes in relation to obesity
Time frame: Two years
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 11 Feb 2020.
- Results publication: PubMed 29313949Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
- Results publication: PubMed 3652025Creasman WT, Morrow CP, Bundy BN, Homesley HD, Graham JE, Heller PB. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987 Oct 15;60(8 Suppl):2035-41. doi: 10.1002/1097-0142(19901015)60:8+3.0.co;2-8.
- Results publication: PubMed 26539494Li X, Gao Y, Tan M, Zhuang H, Gao J, Hu Z, Wang H, Zhu L, Liu J, Lin B. Expression of HE4 in Endometrial Cancer and Its Clinical Significance. Biomed Res Int. 2015;2015:437468. doi: 10.1155/2015/437468. Epub 2015 Oct 11.
- Results publication: PubMed 21468050Bignotti E, Ragnoli M, Zanotti L, Calza S, Falchetti M, Lonardi S, Bergamelli S, Bandiera E, Tassi RA, Romani C, Todeschini P, Odicino FE, Facchetti F, Pecorelli S, Ravaggi A. Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients. Br J Cancer. 2011 Apr 26;104(9):1418-25. doi: 10.1038/bjc.2011.109. Epub 2011 Apr 5.
- Cancer Research UK. Uterine Cancer Statistics.Link provided by the sponsor.
- Group, U.S. Cancer Statistics Working. United States Cancer Statistics: 1999-2014 Incidence and Mortality Web-based Report.Link provided by the sponsor.
- 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.
Tatiana Cuesta-Guardiola, Medicine principal investigator
Hospital de Leon
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 Neoplasm Malignant, run by Fundación Investigación Sanitaria en León at 1 site in Spain.
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 4 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 11 Feb 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 Spain. 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?
The proportion of positive H-score of HE4. (time frame: Two 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 NCT03498924, which also lists 4 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 11 Feb 2020.