Accuracy of the Preoperative Molecular Diagnosis of Uterine Tumors by Liquid Biopsy (MYOSARCII)

Prospective, Observational and Multicenter Case-control Study to Evaluate the Precision of the Preoperative Molecular Diagnosis of Uterine Tumors by Liquid Biopsy

The development of precise and non-invasive diagnostic methods is a priority in areas such as gynaecology and oncology, and above all in improving the health of those patients with a surgical indication for hysterectomy, laparoscopic or laparotomic myomectomy for diagnosis of uterine tumours. Indeed, in the absence of an accurate and objective preoperative diagnostic option, all patients with suspected benign tumours should be considered at risk for occult leiomyosarcoma.

Recently, the concept of "liquid biopsy" has emerged as a minimally invasive alternative to surgical biopsies for solid tumours with highly recurrent mutations, avoiding the sampling of tumour tissue before and after treatment. Generally, the liquid biopsy is obtained by taking a sample of blood or other body fluids, to provide tumour-specific information.

Based on these premises, a prospective, observational and multicentre case-control study is proposed, the objective of which is to evaluate the diagnostic precision (sensitivity, specificity, negative predictive value and positive predictive value) in the detection of molecular differences by liquid biopsy in patients with suspected myometrial tumour (leiomyoma / leiomyosarcoma).

Depending on the results of these analysis, the application of this technology could allow the differential diagnosis of the tumour in a non-invasive and objective way, as well as the development of biomarkers and effective targeted therapies in the treatment of leiomyosarcomas. Consequently, we would also be increasing our knowledge of tumour biology and associated pathologies in a clinical and therapeutic context.

Study Overview

• Status: Recruiting
• Conditions: Leiomyoma, Uterine; Leiomyosarcoma Uterus
• Intervention / Treatment: Procedure: Collection of Leiomyoma samples; Procedure: Collection of Leiomyosarcoma samples; Procedure: Collection of control samples

Detailed Description

Recently, the concept of "liquid biopsy" has emerged as a minimally invasive alternative to surgical biopsies. Generally, the liquid biopsy is obtained by taking a sample of blood or other body fluids, to provide tumour-specific information.

The use of technologies such as high-throughput sequencing or Next Generation Sequencing (NGS) could be an effective method for the detection of molecular differences from circulating genetic material in peripheral blood of patients with suspected myometrial tumour (leiomyoma / leiomyosarcoma), versus patients without tumour pathologies.

This is a prospective, multicentre, national biomedical case-control study aimed at patients with a surgical indication for hysterectomy or myomectomy due to the diagnosis of myometrial tumours (leiomyoma / leiomyosarcoma) according to standard clinical practice.

Once the study is approved by the Research Ethics Committee (CEI) of the Hospital, we will proceed to the recruitment and selection of those patients who meet the inclusion criteria.

After obtaining informed consent, peripheral blood will be collected from the candidate patient, prior to the surgery that the patient had already planned for medical indication in accordance with the usual clinical practice or, in the case of control patients, during an analysis or gynaecological consultation that was already planned to be performed by routine clinical practice. These samples will be sent to the Igenomix Foundation laboratories for molecular study.

Finally, and once both molecular and histological results are obtained, the precision of the determination of the molecular results will be compared with the "gold standard" in the diagnosis of myometrial tumours through two expert evaluators in pathological anatomy.

In this way, if the hypothesis raised is confirmed and the proposed objectives are achieved, we would be demonstrating the viability of a minimally invasive and precise preoperative diagnostic approach, based on the molecular characterization of leiomyoma and leiomyosarcoma.

When calculating the sample size for our study, we have considered the main objective, which is the validation of the test, comparing it with the "gold standard" of pathological anatomy. To calculate the sensitivity and specificity of the test, we would need a minimum of 200 LMS samples, 200 LM samples, and 200 control patient samples for validation.

It is intended to establish a cut-off point with a preliminary analysis in the first 30 patients (10 first patients from each group), in which the laboratory data are combined with those derived from the Pathological Anatomy (Gold Standard).

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: Carlos Gómez, BSc, MSc; Phone Number: +34 963905310; Email: carlos.gomez@igenomix.com

Study Locations

• Spain
  • Alicante, Spain
    • Not yet recruiting
    • Hospital General de Alicante
    • Contact: Maria José Román, MD; Phone Number: +34 965 93 30 00; Email: mjromangine@gmail.com
  • Barcelona, Spain
    • Recruiting
    • Hospital Clinic de Barcelona
    • Contact: Berta Díaz, MD; Phone Number: +34 932 27 54 00; Email: bertadiazfeijoo@gmail.com
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital del Mar Parc Salut
    • Contact: Gemma Mancebo, MD; Phone Number: +34 932 48 30 00; Email: gemmamancebom@gmail.com
  • León, Spain
    • Not yet recruiting
    • Hospital Universitario de Leon
    • Contact: Tatiana Cuesta, MD; Phone Number: +34 987 23 74 00; Email: tguardio@hotmail.com
  • Madrid, Spain
    • Not yet recruiting
    • Hospital MD Anderson Cancer Center Madrid
    • Contact: Javier De Santiago, MD; Phone Number: +34 912 77 72 20; Email: jsantiagog@hotmail.es
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Quiron Madrid
    • Contact: Sara Iacoponi, MD; Phone Number: +34 914 52 19 00; Email: saraiacoponi@hotmail.com
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario 12 de Octubre de Madrid
    • Contact: Blanca Gil, MD; Phone Number: +34 913 90 80 00; Email: blancalabacin@hotmail.com
    • Contact: Alvaro Tejerizo, MD; Phone Number: +34 913 90 80 00; Email: tejerizo@hotmail.com
  • Murcia, Spain
    • Recruiting
    • Hospital Clínico Universitario Virgen de la Arrixaca de Murcia
    • Contact: Aníbal Nieto, MD; Phone Number: +34 968 36 95 00; Email: anibal.nieto@um.es
  • Málaga, Spain
    • Not yet recruiting
    • Hospital Regional Universitario de Malaga
    • Contact: Jesús Jimenez, MD; Phone Number: +34 951 29 00 00; Email: jjimenezme35426@hotmail.com
  • Sevilla, Spain
    • Not yet recruiting
    • Hospital Virgen de la Macarena
    • Contact: Francisco Márquez, MD; Phone Number: +34 955 00 80 00; Email: fmarquezma@gmail.com
  • Toledo, Spain
    • Recruiting
    • Hospital Virgen de la Salud de Toledo
    • Contact: Sara Rojas, MD; Phone Number: +34 925 26 61 00; Email: sararjsrz@gmail.com
  • Valencia, Spain
    • Not yet recruiting
    • Hospital Clinico Universitario de Valencia
    • Contact: Aymara Mas, PhD; Phone Number: +34 961 97 35 00; Email: amas@incliva.es
    • Contact: Octavio Burgues, MD; Phone Number: +34 961 97 35 00; Email: octavioburgues@gmail.com
  • Valencia, Spain
    • Not yet recruiting
    • Hospital General Universitario de Valencia
    • Contact: Juan Gilabert, MD; Phone Number: +34 963 13 18 00; Email: juangilaeste@yahoo.es
    • Contact: Kristina Aghababyan, MD; Phone Number: +34 963 13 18 00; Email: dra.kristina.agababyan@gmail.com
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario y Politecnico la Fe de Valencia
    • Contact: Santiago Domingo, MD; Phone Number: +34 961 24 43 50; Email: santiago.domingo.delpozo@gmail.com
    • Contact: Javier Monleón, MD; Phone Number: +34 961 24 43 50; Email: monlesancho@gmail.com
  • Barcelona
    • L´Hospitalet de Llobregat, Barcelona, Spain
      • Not yet recruiting
      • Hospital Universitari de Bellvitge
      • Contact: Jose Manuel Martínez, MD; Phone Number: +34 932 60 75 00; Email: jmartinezgar@bellvitgehospital.cat
      • Contact: Sergi Fernández, MD; Phone Number: +34 932 60 75 00; Email: sergi.sfg@gmail.com
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain
      • Not yet recruiting
      • Hospital Universitario de Son LLàtzer de Mallorca
      • Contact: Albert Reyes, MD; Phone Number: +34 871 20 20 00; Email: areyes1@hsll.es
      • Contact: Cristina Martínez, MD; Phone Number: +34 871 20 20 00; Email: mcmartinez@hsll.es
  • Las Palmas
    • Las Palmas De Gran Canaria, Las Palmas, Spain
      • Not yet recruiting
      • Complejo Hospitalario Universitario Insular de Las Palmas
      • Contact: Miguel Andújar, MD; Phone Number: +34 928 44 40 00; Email: mandsan@gobiernodecanarias.org
      • Contact: Octavio Arencibia, MD; Phone Number: +34 928 44 40 00; Email: octavaren@hotmail.com
  • Madrid
    • Getafe, Madrid, Spain
      • Not yet recruiting
      • Hospital Universitario de Getafe
      • Contact: Belén Martín, MD; Phone Number: +34 916 83 93 60; Email: belenmsalamanca@yahoo.com
    • Majadahonda, Madrid, Spain
      • Not yet recruiting
      • Hospital Universitario Puerta de Hierro Majadahonda
      • Contact: Tirso Pérez, MD; Phone Number: +34 911 91 60 00; Email: tirsoperezmedina@gmail.com
      • Contact: Augusto Pereira, MD; Phone Number: +34 911 91 60 00; Email: augusto.pereira@salud.madrid.org
  • Murcia
    • Cartagena, Murcia, Spain
      • Not yet recruiting
      • Complejo Hospitalario de Cartagena
      • Contact: Sebastián Ortiz, MD; Phone Number: +34 968 12 86 00; Email: sortizreina@yahoo.es
  • Navarra
    • Pamplona, Navarra, Spain
      • Not yet recruiting
      • Complejo Hospitalario de Navarra
      • Contact: Juan Carlos Muruzabal, MD; Phone Number: 59958 +34 848 42 22 22; Email: jc.muruzabal.torquemada@navarra.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women between 18 and 80 years old and with a body mass index (BMI) of 18.5-40.0 kg / m2, with suspected myometrial tumour (leiomyoma / leiomyosarcoma) based on clinical symptoms and imaging diagnosis, will be evaluated in their referral centre, verifying that they meet the inclusion / exclusion criteria to participate in the study. Women with the same age and BMI but without a uterine tumour will be used as control patients.

Description

Inclusion Criteria:

• Patients who voluntarily sign the informed consent approved by the Research Ethics Committee (CEI) after having been duly informed of the nature of the study, before carrying out any test related to it, knowing the potential risks, benefits and discomforts derived from their participation. Participants should be informed that they may leave the study at any time, without this entailing any consequence for their subsequent medical care.
• BMI = 18.5-40 kg / m2
• Age = 18-80 years
• Surgical indication according to usual clinical practice, due to suspicion of a tumour mass in the uterus, either primary (stages I-IV) or recurrence, but without prior chemotherapy or radiotherapy (at the time of primary diagnosis or prior to recurrence) .
• Note: Control patients will have the same inclusion criteria for BMI and age but without uterine tumour pathology.

Exclusion Criteria:

• Patients who have participated in a clinical trial during the last 30 days unless it is approved by the sponsor as it does not interfere with the current study.
• Patients who have received chemotherapy or radiotherapy before taking the sample (in case of recurrence).
• Pregnant patients before or during the duration of the study.
• Existence of serious or uncontrolled bacterial, fungal, or viral infections (type HPV, HIV, hepatitis) that, in the opinion of the principal investigator, could interfere with the participation of the patient in the study or in the evaluation of the study results.
• Any disease or medical condition that is unstable or may jeopardize patient safety and compliance in the study. For example: patients with an active history of other malignant tumours.
• Psychological, family, sociological or geographical situations that do not allow compliance with the protocol or the signing of informed consent.
• Patients vaccinated with mRNA vaccines in the week before surgery.
• Note: Control patients will have the same exclusion criteria as patients with tumour pathology

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Leiomyoma samples; Leiomyoma samples and peripheral blood samples obtained from women between 18 and 80 years with suspected myometrial tumour	Procedure: Collection of Leiomyoma samples; Peripheral blood will be collected from the candidate patient with suspected myometrial tumours, prior to the surgery already planned form medical indication in accordance with routine clinical practice. A sample of tumour tissue will be collected during surgery and sent to pathologists for diagnosis in accordance with the usual clinical practice. The tumour paraffin block/sections will be requested for the study only after the diagnosis.; Other Names: Obtainment of blood sample (peripheral blood) and tumour tissue sample
Leiomyosarcoma samples; Leiomyosarcoma samples and peripheral blood samples obtained from women between 18 and 80 years with suspected myometrial tumour	Procedure: Collection of Leiomyosarcoma samples; Peripheral blood will be collected from the candidate patient with suspected myometrial tumours, prior to the surgery already planned form medical indication in accordance with routine clinical practice. A sample of tumour tissue will be collected during surgery and sent to pathologists for diagnosis in accordance with the usual clinical practice. The tumour paraffin block/sections will be requested for the study only after the diagnosis.; Other Names: Obtainment of blood sample (peripheral blood) and tumour tissue sample
Control samples; Peripheral blood samples obtained from women between 18 and 80 years without suspected myometrial tumour	Procedure: Collection of control samples; Peripheral blood will be collected during an analysis or gynaecological consultation already planned by routine clinical practice. The sample will be sent to Igenomix for molecular analysis.; Other Names: Obtainment of blood sample (peripheral blood)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic precision of uterine tumours at molecular level	Sensitivity, specificity, negative predictive value and positive predictive value of the molecular diagnosis of uterine tumours by liquid biopsy as a preoperative diagnosis, using pathological diagnosis as a "gold standard" to validate the molecular diagnosis.	25 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance of Circulating tumour DNA / RNA versus DNA / RNA in tumour	Determine the concordance of circulating tumour DNA / RNA in plasma (ctRNA / ctDNA) versus the contribution of tumour tissue DNA / RNA in determining the diagnosis and histological subtype	25 months
Inter-observer variability	Inter-observer variability in determining the histological diagnosis of uterine tumours in the analysis performed by pathologists	25 months
Evaluation of Circulating tumour DNA / RNA profile for oncological outcome	Contribution of the plasma circulating tumour DNA / RNA profile (ctRNA / ctDNA) in determining the oncological outcome (survival, disease-free interval)	25 months

Collaborators and Investigators

• Sponsor: Igenomix
• Investigators: Principal Investigator: Aymara Mas, PhD, Igenomix Foundation

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 21, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Sarcoma; Next Generation Sequencing; Leiomyoma (LM); Leiomyosarcoma (LMS); Circulating tumour cells (CTC); Plasma cell-free RNA (cfRNA)
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Sarcoma; Neoplasms, Muscle Tissue; Leiomyosarcoma; Leiomyoma; Myofibroma
• Other Study ID Numbers: IGX1-DTU-AM-21-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No