## Protocol Section
### Identification Module
**NCT ID:** NCT06083779

**Brief Title:** Early Detection of Endometrial Cancer Using Plasma Cell-free DNA Fragmentomics

**Official Title:** A Prospective Study of Early Detection of Endometrial Cancer Using Plasma Cell-free DNA Fragmentomics

#### Organization Study ID Info
**ID:** SYSKY-2023-848-01
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
### Status Module
#### Completion Date
**Date:** 2024-04-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-10-16

**Type:** ACTUAL

**Last Update Submit Date:** 2023-10-09

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-01-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-08-01

**Type:** ACTUAL

**Status Verified Date:** 2023-08

#### Study First Post Date
**Date:** 2023-10-16
**Type:** ACTUAL
**Study First Submit Date:** 2023-10-09
**Study First Submit QC Date:** 2023-10-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Nanjing Geneseeq Technology Inc.

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to enable non-invasive early detection of endometrial cancer in high-risk populations through the establishment of a multimodal machine learning model using plasma cell-free DNA fragmentomics. Plasma cell-free DNA from early stage endometrial cancer patients and healthy individuals will be subjected to whole-genome sequencing. Five different feature types, including Fragment Size Distribution, nucleosome features, SBS Signatures, BreakPoint Motif , and Copy Number Variation will be assessed to generate this model.

**Detailed Description:** Currently, there is no international consensus on the standard for endometrial cancer screening. The Expert Committee on Endometrial Cancer Screening in China released the "Expert Consensus on Endometrial Cancer Screening and Early Diagnosis (Draft)" in 2017, recommending the use of endometrial brushes for endometrial sampling and the use of endometrial cytology for slide preparation. Transvaginal ultrasound (TVS) can be used as an initial assessment and auxiliary method for endometrial cytology screening for endometrial cancer. For women without clinical symptoms, the routine method of endometrial cancer screening is mainly TVS to monitor endometrial thickness. Although TVS has high sensitivity, its specificity is very low, with a low positive predictive value (PPV) and a high false-positive rate, making it unable to distinguish between benign and malignant endometrial changes. There are also certain operator subjective judgments and instrument-related errors. For women with clinical symptoms, patients need endometrial cytology testing, that is, invasive endometrial sampling with an endometrial brush, followed by cytological slide preparation. Suspicious malignant tumor cells or malignant tumor cells should immediately undergo hysteroscopy and segmental diagnostic curettage to obtain endometrial biopsy tissue, and further clinical treatment should be carried out based on the pathological results. Due to the need to go deep into the uterus, the sampling failure rate for nulliparous women is as high as 20%, and the sampling failure rate for multiparous women is 8%. Whether it is endometrial cytology or hysteroscopic biopsy, which is close to the invasive operation of abortion, it will bring a lot of pain and economic burden to women. Moreover, there are currently no specific and sensitive tumor markers available for the diagnosis and follow-up of endometrial cancer. Therefore, it is urgent to develop a non-invasive, efficient screening detection method.

In short, the space for early screening of endometrial cancer is vast, and liquid biopsy is non-invasive, convenient and easy to accept. It is an important technical means for early screening research of endometrial cancer, and has great potential to improve the performance of early screening of endometrial cancer. In order to further verify the application value of cfDNA-based fragmentomics in early screening of endometrial cancer and better screen the high-risk population of endometrial cancer in China, this study intends to analyze the characteristics of five cfDNA fragments based on low-depth whole-genome sequencing technology (WGS), and integrate artificial intelligence machine learning technology to establish a prediction model for early screening of endometrial cancer based on cfDNA.

### Conditions Module

**Conditions:**

- Endometrial Cancer

**Keywords:**

- Endometrial Cancer

- Early Stage

- Plasma Cell-free DNA

- Fragmentomic assay

### Design Module

#### Bio Spec

**Description:** Plasma Cell-free DNA

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** CASE_CONTROL

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 216

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** the 108 patients with early to mid-stage endometrial cancer, more than 50% were in FIGO stages I/II.

**Intervention Names:**

- Genetic: low-depth whole-genome sequencing technology

**Label:** Patients with endometrial cancer

#### Arm Group 2

**Description:** 108 healthy people

**Intervention Names:**

- Genetic: low-depth whole-genome sequencing technology

**Label:** healthy people

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Patients with endometrial cancer

- healthy people

**Description:** the characteristics of five cfDNA fragments based on low-depth whole-genome sequencing technology (WGS)

**Name:** low-depth whole-genome sequencing technology

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** The area under curve of the model for the ultrasensitive early detection of endometrial cancer would be evaluate

**Measure:** Area under curve of the model for detecting endometrial cancer

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Age minimum 18 years
* Patients diagnosed with early to mid-stage endometrial cancer (more than 50% are in FIGO stages I/II) through histological and/or cytological examination.
* Ability to understand and the willingness to sign a written informed consent document
* Participants can obtain comprehensive clinical and pathological information.
* Non-cancer controls are sex- and age-matched individuals without presence of any tumors or nodules or any other severe chronic diseases through systematic screening

Exclusion Criteria:

* Participants must not be pregnant or breastfeeding
* Participants must not have prior cancer histories or a second non-endometrial malignancy
* Participants must not have had any form of cancer treatment before enrollment or plasma collection, including surgery, chemotherapy, radiotherapy, targeted therapy and immunotherapy
* Participants must not present medical conditions of fever or have acute or immunological diseases that required treatment 14 days before plasma collection
* Participants who underwent organ transplant or allogenic bone marrow or hematopoietic stem cell transplantation
* Participants with clinically important abnormalities or conditions unsuitable for blood collection
* Any other disease or clinical condition of participants that the researcher believes may affect the compliance of the protocol, or affect the patient's signing of the informed consent form (ICF), which is not suitable to participate in this clinical trial.

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Approximately 108 early to mid-stage endometrial cancer patients and 108 non-cancer controls

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 13925063030@163.com

**Name:** Bingzhong Zhang, MD

**Phone:** 13925063030

**Phone Ext:** 86

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Email:** 13925063030@163.com

- **Name:** Bingzhong Zhang, MD

- **Phone:** 13925063030

- **Phone Ext:** 86

- **Role:** CONTACT

**Country:** China

**Facility:** The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

**State:** Guangdong

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** The Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

**Name:** Bingzhong Zhang, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014594

- Term: Uterine Neoplasms

- ID: D000005833

- Term: Genital Neoplasms, Female

- ID: D000014565

- Term: Urogenital Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000014591

- Term: Uterine Diseases

- ID: D000005831

- Term: Genital Diseases, Female

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000091662

- Term: Genital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M19235

- Name: Endometrial Neoplasms

- Relevance: HIGH

- As Found: Endometrial Cancer

- ID: M17342

- Name: Uterine Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8945

- Name: Genital Neoplasms, Female

- Relevance: LOW

- As Found: Unknown

- ID: M17315

- Name: Urogenital Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M17339

- Name: Uterine Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8943

- Name: Genital Diseases, Female

- Relevance: LOW

- As Found: Unknown

- ID: M2876

- Name: Genital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016889

- Term: Endometrial Neoplasms

### Misc Info Module

- Version Holder: 2024-05-24
