Development of a Molecular Diagnostic Tool for Endometrial Cancer.

Endometrium Cancer Clinical Trial

Official title:

Development of a Molecular Diagnostic Tool for Endometrial Cancer.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06192017
• Other study ID #: WomEC SEGO
• Status: Recruiting
• Start date: October 18, 2023
• Est. completion date: October 17, 2024

Study information

• Verified date: January 2024
• Source: MiMARK Diagnostics, S.L.
• Contact: Antonio Gil-Moreno, MD, PhD
• Phone: 934893066
• Email: antonio.gil[@]vallhebron.cat
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

WomEC is an in vitro diagnostic test for Endometrial Cancer (EC) based on the detection of the expression level of a combination of 5 proteins in the soluble fraction of a pipelle biopsy specimen. The aim of the study consists in validating WomEC's ELISA test, creating and freezing an algorithm to rule out EC in post-menopausal women with abnormal uterine bleeding (AUB).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: October 17, 2024
• Est. primary completion date: October 17, 2024
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Post-menopausal women (=1 year without menstruation) with AUB who present with:

1. Endometrium > 3mm by transvaginal ultrasound, OR

2. Endometrium = 3mm who meet at least one of the following criteria:

i. Persistent symptoms (more than one episode of metrorrhagia) ii. Heterogenous endometrium on transvaginal ultrasonography iii. Risk factors (BMI = 30, use of tamoxifen, hormone replacement therapy (HRT), Lynch syndrome, BRCA mutation.

• Obtaining written informed consent

Exclusion Criteria:

• Women with an active pelvic infection.
• Women who have had viral infections with evidence of active and latent disease such as Hepatitis B, Hepatitis C, and HIV infection. Patients who have had Hepatitis C in the past but who have been successfully treated and in whom viral replication has not been observed in the last year will be included.

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Endometrium Cancer

Intervention

Diagnostic Test:
• WomEC
The study will collect pipelle biopsies from post-menopausal women presenting with AUB entering to the EC diagnostic process at the clinical consultancy or emergency room. In the study an endometrial biopsy by aspiration will be collected (i.e., pipelle biopsy) and it will be used for (1) diagnostic purposes following current procedures (i.e., pathological examination and diagnosis); (2) placed in a collection tube for WomEC test.

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona
Spain	Hospital Universitari Campus Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Puerto Real	Cadiz
Spain	Hospital General Universitari de Castelló	Castelló de la Plana
Spain	Hospital Universitario de Donostia	Donostia	Guipuzcoa
Spain	Hospital Universitario de Getafe	Getafe	Madrid
Spain	Hospital Universitari de Bellvitge - Hospital Duran i Reynals	Hospitalet de Llobregat	Barcelona
Spain	Hospital Materno Infantil de Gran Canaria	Las Palmas De Gran Canaria	Las Palmas
Spain	Hospital Universitario de León	León
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Hospital Universitari Son Espases	Palma De Mallorca	Balearic Islands
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario de Torrevieja	Torrevieja	Alicante
Spain	Hospital General Universitari de València	Valencia
Spain	Hospital Universitario y Politécnico de La Fe	Valencia
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
MiMARK Diagnostics, S.L.	Hospital Vall d'Hebron

Country where clinical trial is conducted

Spain, 

References & Publications (16)

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Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women: A Systematic Review and Meta-analysis. JAMA Intern Med. 2018 Sep 1;178(9):1210-1222. doi: 10.1001/jamainternmed.2018.2820. — View Citation

Colas E, Perez C, Cabrera S, Pedrola N, Monge M, Castellvi J, Eyzaguirre F, Gregorio J, Ruiz A, Llaurado M, Rigau M, Garcia M, Ertekin T, Montes M, Lopez-Lopez R, Carreras R, Xercavins J, Ortega A, Maes T, Rosell E, Doll A, Abal M, Reventos J, Gil-Moreno A. Molecular markers of endometrial carcinoma detected in uterine aspirates. Int J Cancer. 2011 Nov 15;129(10):2435-44. doi: 10.1002/ijc.25901. Epub 2011 Apr 8. Erratum In: Int J Cancer. 2012 Jun 15;130(12):E4. — View Citation

DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988 Sep;44(3):837-45. — View Citation

Dueholm M, Hjorth IMD, Dahl K, Hansen ES, Ortoft G. Ultrasound Scoring of Endometrial Pattern for Fast-track Identification or Exclusion of Endometrial Cancer in Women with Postmenopausal Bleeding. J Minim Invasive Gynecol. 2019 Mar-Apr;26(3):516-525. doi: 10.1016/j.jmig.2018.06.010. Epub 2018 Jun 23. — View Citation

Fawcett T. An introduction to ROC analysis. Pattern Recognit Lett. North-Holland; 2006;27:861-74.

Helpman L, Kupets R, Covens A, Saad RS, Khalifa MA, Ismiil N, Ghorab Z, Dube V, Nofech-Mozes S. Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer. Br J Cancer. 2014 Feb 4;110(3):609-15. doi: 10.1038/bjc.2013.766. Epub 2013 Dec 24. — View Citation

Martinez-Garcia E, Lesur A, Devis L, Cabrera S, Matias-Guiu X, Hirschfeld M, Asberger J, van Oostrum J, Casares de Cal MLA, Gomez-Tato A, Reventos J, Domon B, Colas E, Gil-Moreno A. Targeted Proteomics Identifies Proteomic Signatures in Liquid Biopsies of the Endometrium to Diagnose Endometrial Cancer and Assist in the Prediction of the Optimal Surgical Treatment. Clin Cancer Res. 2017 Nov 1;23(21):6458-6467. doi: 10.1158/1078-0432.CCR-17-0474. Epub 2017 Aug 8. — View Citation

Martinez-Garcia E, Lesur A, Devis L, Campos A, Cabrera S, van Oostrum J, Matias-Guiu X, Gil-Moreno A, Reventos J, Colas E, Domon B. Development of a sequential workflow based on LC-PRM for the verification of endometrial cancer protein biomarkers in uterine aspirate samples. Oncotarget. 2016 Aug 16;7(33):53102-53115. doi: 10.18632/oncotarget.10632. — View Citation

Martinez-Garcia E, Lopez-Gil C, Campoy I, Vallve J, Coll E, Cabrera S, Ramon Y Cajal S, Matias-Guiu X, Van Oostrum J, Reventos J, Gil-Moreno A, Colas E. Advances in endometrial cancer protein biomarkers for use in the clinic. Expert Rev Proteomics. 2018 Jan;15(1):81-99. doi: 10.1080/14789450.2018.1410061. Epub 2017 Nov 30. — View Citation

Perez-Sanchez C, Colas E, Cabrera S, Falcon O, Sanchez-del-Rio A, Garcia E, Fernandez-de-Castillo L, Muruzabal JC, Alvarez E, Fiol G, Gonzalez C, Torrejon R, Moral E, Campos M, Repolles M, Carreras R, Jimenez-Lopez J, Xercavins J, Aibar E, Perdones-Montero A, Lalanne E, Palicio M, Maes T, Rosell-Vives E, Nieto C, Ortega A, Pedrola N, Llaurado M, Rigau M, Doll A, Abal M, Ponce J, Gil-Moreno A, Reventos J. Molecular diagnosis of endometrial cancer from uterine aspirates. Int J Cancer. 2013 Nov 15;133(10):2383-91. doi: 10.1002/ijc.28243. Epub 2013 Jun 21. — View Citation

Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011 Mar 17;12:77. doi: 10.1186/1471-2105-12-77. — View Citation

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022 Jan;72(1):7-33. doi: 10.3322/caac.21708. Epub 2022 Jan 12. — View Citation

van Hanegem N, Prins MM, Bongers MY, Opmeer BC, Sahota DS, Mol BW, Timmermans A. The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2016 Feb;197:147-55. doi: 10.1016/j.ejogrb.2015.12.008. Epub 2015 Dec 19. — View Citation

Visser NCM, Reijnen C, Massuger LFAG, Nagtegaal ID, Bulten J, Pijnenborg JMA. Accuracy of Endometrial Sampling in Endometrial Carcinoma: A Systematic Review and Meta-analysis. Obstet Gynecol. 2017 Oct;130(4):803-813. doi: 10.1097/AOG.0000000000002261. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Regulatory Requirements Study	Ensure the stability of the samples under defined conditions (pre-analytica) and the analytical validation of the developed WomEC's ELISA test.	12 months
Primary	Algorithm training with Proprietary Antibodies	Train the current WomEC's algorithms defined in MS by assessing the clinical performance of different EC biomarkers individually and in combination to rule out EC in post- menopausal women with AUB using MiMARK's proprietary antibodies.	12 months
Primary	Algorithm testing and freeze	To test and freeze the defined algorithm measured with MiMARK's antibodies to rule out EC in post-menopausal women with AUB.	12 months
Secondary	To determine the accuracy of WomEC alone for the diagnosis of EC by pipelle biopsy.	Test the ability of WomEC to discriminate between EC and non-EC patients.	12 months
Secondary	Evaluation of the performance of different models of WomEC to determine histological subtype.	Calculate the sensitivity, specificity, accuracy, precision, and clinical validity of WomEC to determine an histological subtype.	12 months
Secondary	Evaluation of the performance of WomEC to determine other prognostic factors of EC.	Calculate the sensitivity, specificity, accuracy, precision, and clinical validity of WomEC to determine other prognostic factors of EC.	12 months
Secondary	Evaluation of the performance of WomEC to diagnose endometrial atypical hyperplasia.	Calculate the sensitivity, specificity, accuracy, precision, and clinical validity of WomEC to diagnose endometrial atypical hyperplasia.	12 months