## Protocol Section
### Identification Module
**NCT ID:** NCT05955079

**Acronym:** ctDNA-endo

**Brief Title:** Circulating Tumor DNA Study in Patients With Endometrial Cancer

**Official Title:** Prospective Validation of the Association Between Circulating Tumor DNA Detection and Risk of Metastatic Relapse in Patients With Localized Endometrial Cancer

#### Organization Study ID Info
**ID:** CRC22003
#### Organization
**Class:** OTHER
**Full Name:** Assistance Publique - Hôpitaux de Paris
#### Secondary ID Infos
**Domain:** AP-HP
**ID:** 20200812151455
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2026-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-07-21

**Type:** ACTUAL

**Last Update Submit Date:** 2023-07-12

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-01-01

**Type:** ACTUAL

**Status Verified Date:** 2023-05

#### Study First Post Date
**Date:** 2023-07-21
**Type:** ACTUAL
**Study First Submit Date:** 2023-07-12
**Study First Submit QC Date:** 2023-07-12
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** CARPEM, Institut du Cancer Paris

**Class:** UNKNOWN

**Name:** Centre de recherche des Cordeliers

**Class:** UNKNOWN

**Name:** METHYS DX

#### Lead Sponsor

**Class:** OTHER

**Name:** Assistance Publique - Hôpitaux de Paris

#### 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 objective of this study is to identify a population at risk of early recurrence after oncologic resection surgery of a primary uterine tumor based on the detection of ctDNA

**Detailed Description:** Despite early management, the risk of recurrence in non-metastatic endometrial cancer (FIGO I-III) is approximately 10-20%. The challenge is to identify the most high-risk cases for relapse in order to adapt surgical and medical management.

The development of digital PCR methods in nano-droplets, detecting circulating tumor DNA (ctDNA) with high sensitivity, could help to better specify the prognosis of patients with localized endometrial cancer and to identify a population with residual disease, the source of this ctDNA.

The investigators established a universal methylation signature in the laboratory based on analysis of endometrial cancer-specific DNA methylation using in silico analysis of public data from the Cancer Genome Atlas, validated in an independent cohort, with 99% sensitivity and 98% specificity.

A prospective biological cohort was established between the gynecology and medical oncology departments and the Cochin Hospital biological resources center (CARPEM-OncoCentre collection).

This is a prospective monocentric biological collection study.

The aim of this study is to evaluate the prognostic impact of pre- and post-operative ctDNA detection in stage I-III endometrial cancer.

### Conditions Module

**Conditions:**

- Endometrial Cancer

**Keywords:**

- Endometrial Cancer

- Digital-PCR

- Circulating Tumor DNA

- minimal residual disease

- liquid biopsy

### Design Module

#### Bio Spec

**Description:** Whole blood, three samples (before, after surgery and before chemotherapy)

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 130

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients over 18 years old with a biopsy-proven endometrial cancer, at FIGO stage I to IV, and amenable and undergoing surgical treatment

**Intervention Names:**

- Other: Whole blood

**Label:** Endometrial Cancer

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Endometrial Cancer

**Description:** 3 samples (before, after surgery and before chemotherapy)

**Name:** Whole blood

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Measure:** Recurrence-free survival

**Time Frame:** 1 year

#### Secondary Outcomes

**Measure:** Recurrence-free survival

**Time Frame:** 3 years

**Description:** Frequency of ctDNA detection based on established prognostic parameters: histological type (endometrioid, non-endometrioid), grade (low grade, high grade), stage (localized to the uterus stages I-II or stage III with nodal involvement), lymphovascular invasion (present/absent), and molecular group (low risk: POLE, intermediate risk: MSI/NSMP, high risk: TP53).

**Measure:** Frequency of ctDNA detection based on established prognostic parameters

**Time Frame:** 3 years

**Description:** Frequency of ctDNA detection in other prognostic groups according to the 2021 ESGO-ESTRO-ESP classification

**Measure:** Frequency of ctDNA detection in other prognostic groups

**Time Frame:** 3 years

**Description:** Frequency of ctDNA detection based on the recurrence profile : anatomical (locoregional versus distant; abdominal versus extra-abdominal; visceral or nodal) or dynamic (aggressive recurrence (progression-free survival post recurrence \<6 months) or non-aggressive (\>6 months))

**Measure:** Frequency of ctDNA detection based on the recurrence profile

**Time Frame:** 3 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Female patients over 18 years of age who are potentially eligible for inclusion in the OncoCentre collection (registered as a patient at APHP, without legal protection measures, affiliated with a social security system)
* Patients diagnosed with histologically documented endometrial cancer on an endometrial biopsy
* Surgical intervention performed at Hopital Cochin

Exclusion Criteria:

* Failure to sign the OncoCentre consent form
* Refusal of OncoCentre consent
* Patient not eligible for upfront curative surgical treatment

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Women undergoing clinically-indicated hysterectomy for endometrial cancer at the University Paris Cité hospital Cochin, who are age 18 years and older

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** guillaume.beinse@aphp.fr

**Name:** Guillaume BEINSE, MD, PhD

**Phone:** +33 1 58 41 14 54

**Role:** CONTACT

**Contact 2:**

**Email:** laetitia.peaudecerf@aphp.fr

**Name:** Laetitia PEAUDECERF

**Phone:** +33 1 58 41 12 13

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Email:** guillaume.beinse@aphp.fr

- **Name:** BEINSE Guillaume, MD, PhD

- **Phone:** +33 1 58 41 14 54

- **Role:** CONTACT

***Contact 2:***

- **Email:** antoine.gaudetchardonnet@aphp.fr

- **Name:** GAUDET CHARDONNET Antoine, MD

- **Phone:** +33 1 58 41 36 61

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital Cochin

**Status:** RECRUITING

**Zip:** 75014

#### Overall Officials

**Official 1:**

**Affiliation:** Assistance Publique - Hôpitaux de Paris

**Name:** Bruno BORGHESE, MD, PhD

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Assistance Publique - Hôpitaux de Paris

**Name:** Jérôme ALEXANDRE, MD, PhD

**Role:** STUDY_CHAIR

### References Module

#### References

**Citation:** Beinse G, Borghese B, Metairie M, Just PA, Poulet G, Garinet S, Parfait B, Didelot A, Bourreau C, Agueeff N, Lavolle A, Terris B, Chapron C, Goldwasser F, Leroy K, Blons H, Laurent-Puig P, Taly V, Alexandre J. Highly Specific Droplet-Digital PCR Detection of Universally Methylated Circulating Tumor DNA in Endometrial Carcinoma. Clin Chem. 2022 Jun 1;68(6):782-793. doi: 10.1093/clinchem/hvac020.

**PMID:** 35323926

**Citation:** Lu KH, Broaddus RR. Endometrial Cancer. N Engl J Med. 2020 Nov 19;383(21):2053-2064. doi: 10.1056/NEJMra1514010. No abstract available.

**PMID:** 33207095

**Citation:** Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. Lancet. 2016 Mar 12;387(10023):1094-1108. doi: 10.1016/S0140-6736(15)00130-0. Epub 2015 Sep 6.

**PMID:** 26354523

**Citation:** Cancer Genome Atlas Research Network; Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Integrated genomic characterization of endometrial carcinoma. Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113. Erratum In: Nature. 2013 Aug 8;500(7461):242.

**PMID:** 23636398

**Citation:** Leon-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, Nijman HW, Singh N, Pollock PM, Bessette P, Fyles A, Haie-Meder C, Smit VTHBM, Edmondson RJ, Putter H, Kitchener HC, Crosbie EJ, de Bruyn M, Nout RA, Horeweg N, Creutzberg CL, Bosse T; TransPORTEC consortium. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol. 2020 Oct 10;38(29):3388-3397. doi: 10.1200/JCO.20.00549. Epub 2020 Aug 4.

**PMID:** 32749941

**Citation:** Kommoss S, McConechy MK, Kommoss F, Leung S, Bunz A, Magrill J, Britton H, Kommoss F, Grevenkamp F, Karnezis A, Yang W, Lum A, Kramer B, Taran F, Staebler A, Lax S, Brucker SY, Huntsman DG, Gilks CB, McAlpine JN, Talhouk A. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Ann Oncol. 2018 May 1;29(5):1180-1188. doi: 10.1093/annonc/mdy058.

**PMID:** 29432521

**Citation:** Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, Marth C, Nout R, Querleu D, Mirza MR, Sessa C; ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann Oncol. 2016 Jan;27(1):16-41. doi: 10.1093/annonc/mdv484. Epub 2015 Dec 2. Erratum In: Ann Oncol. 2017 Jul 1;28(suppl_4):iv167-iv168.

**PMID:** 26634381

**Citation:** de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jurgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2. Epub 2018 Feb 12. Erratum In: Lancet Oncol. 2018 Apr;19(4):e184.

**PMID:** 29449189

**Citation:** Corcoran RB, Chabner BA. Application of Cell-free DNA Analysis to Cancer Treatment. N Engl J Med. 2018 Nov 1;379(18):1754-1765. doi: 10.1056/NEJMra1706174. No abstract available.

**PMID:** 30380390

**Citation:** Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, Anagnostou V, Fiksel J, Cristiano S, Papp E, Speir S, Reinert T, Orntoft MW, Woodward BD, Murphy D, Parpart-Li S, Riley D, Nesselbush M, Sengamalay N, Georgiadis A, Li QK, Madsen MR, Mortensen FV, Huiskens J, Punt C, van Grieken N, Fijneman R, Meijer G, Husain H, Scharpf RB, Diaz LA Jr, Jones S, Angiuoli S, Orntoft T, Nielsen HJ, Andersen CL, Velculescu VE. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017 Aug 16;9(403):eaan2415. doi: 10.1126/scitranslmed.aan2415.

**PMID:** 28814544

**Citation:** Bolivar AM, Luthra R, Mehrotra M, Chen W, Barkoh BA, Hu P, Zhang W, Broaddus RR. Targeted next-generation sequencing of endometrial cancer and matched circulating tumor DNA: identification of plasma-based, tumor-associated mutations in early stage patients. Mod Pathol. 2019 Mar;32(3):405-414. doi: 10.1038/s41379-018-0158-8. Epub 2018 Oct 12.

**PMID:** 30315273

**Citation:** Shintani D, Hihara T, Ogasawara A, Sato S, Yabuno A, Tai K, Fujiwara K, Watanabe K, Hasegawa K. Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer. Int J Gynecol Cancer. 2020 Sep;30(9):1340-1346. doi: 10.1136/ijgc-2019-001053. Epub 2020 Jul 21.

**PMID:** 32699017

**Citation:** Taieb J, Taly V, Henriques J, Bourreau C, Mineur L, Bennouna J, Desrame J, Louvet C, Lepere C, Mabro M, Egreteau J, Bouche O, Mulot C, Hormigos K, Chaba K, Mazard T, de Gramont A, Vernerey D, Andre T, Laurent-Puig P. Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: a Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France Trial. Clin Cancer Res. 2021 Oct 15;27(20):5638-5646. doi: 10.1158/1078-0432.CCR-21-0271. Epub 2021 Jun 3.

**PMID:** 34083233

**Citation:** Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013 Mar 28;153(1):38-55. doi: 10.1016/j.cell.2013.03.008.

**PMID:** 23540689

**Citation:** Garrigou S, Perkins G, Garlan F, Normand C, Didelot A, Le Corre D, Peyvandi S, Mulot C, Niarra R, Aucouturier P, Chatellier G, Nizard P, Perez-Toralla K, Zonta E, Charpy C, Pujals A, Barau C, Bouche O, Emile JF, Pezet D, Bibeau F, Hutchison JB, Link DR, Zaanan A, Laurent-Puig P, Sobhani I, Taly V. A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. Clin Chem. 2016 Aug;62(8):1129-39. doi: 10.1373/clinchem.2015.253609. Epub 2016 Jun 1.

**PMID:** 27251038

**Citation:** Kint S, De Spiegelaere W, De Kesel J, Vandekerckhove L, Van Criekinge W. Evaluation of bisulfite kits for DNA methylation profiling in terms of DNA fragmentation and DNA recovery using digital PCR. PLoS One. 2018 Jun 14;13(6):e0199091. doi: 10.1371/journal.pone.0199091. eCollection 2018.

**PMID:** 29902267

#### See Also Links

**Label:** Related Info

**URL:** https://carpem.fr/activites/les-plateformes/biobanques/projets-de-recherche-collection-oncocentre/

## 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: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

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

### Condition Browse Module - Browse Leaves

- ID: M20497

- Name: Neoplasm, Residual

- Relevance: LOW

- As Found: Unknown

- 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
