ctDNA Testing to Inform Standard-of-Care Treatment Decisions in People With Endometrial Cancer

Pragmatic Pilot Study of ctDNA Informed Immune Checkpoint Inhibitor De-escalation in Advanced/Recurrent Mismatch Repair Deficient (MMR-D)/Microsatellite Instability High (MSI-H) Endometrial Cancer Using Standard of Care Treatments

The researchers are doing this study to evaluate the use of circulating tumor DNA (ctDNA) testing in making treatment decisions for advanced/recurrent endometrial cancer that has a change (mutation) in the mismatch repair deficient (MMR-D) gene or microsatellite instability high (MSI-H) gene. The researchers will see how doctors and their patients use the results of ctDNA testing after 1 year of standard chemotherapy and immune checkpoint inhibitor (ICI) treatment to decide whether to continue maintenance ICI treatment past 1 year. The researchers will also look at the health outcomes of people in this study (for example, whether they are cancer free at the end of their participation in the study).

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Genetic: ctDNA Testing; Other: Blood draw; Other: Surveys; Other: Semi-structured interviews

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ying Liu, MD, MPH; Phone Number: 646-888-4946; Email: liuy6@mskcc.org
• Study Contact Backup: Name: Paul Johannet, MD; Phone Number: 646-888-5327

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (All Protocol Activites)
      • Contact: Ying Liu, MD; Phone Number: 646-888-4946
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (All Protocol Activities)
      • Contact: Ying Liu, MD; Phone Number: 646-888-4946
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (All Protocol Activities)
      • Contact: Ying Liu, MD; Phone Number: 646-888-4946
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (All Protocol Activities)
      • Contact: Ying Liu, MD; Phone Number: 646-888-4946
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (All Protocol Activities)
      • Contact: Ying Lui, MD; Phone Number: 646-888-4946
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Roisin O'Cearbhaill, MD; Phone Number: 646-888-4227
      • Contact: Ying Liu, MD, MPH.; Phone Number: 646-888-4946
    • Rockville Centre, New York, United States, 11570
      • Recruiting
      • Memorial Sloan Kettering Nassau (All Protocol Activities)
      • Contact: Ying Liu, MD; Phone Number: 646-888-4946

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have pathologically confirmed endometrial cancer
• Patients with advanced endometrial cancer

• Stage III with residual disease

  °Select patients with Stage III disease and no residual disease can be enrolled after discussion with PI

• Stage IV
• Recurrent endometrial cancer after adjuvant therapy only
• Patients can have primary or planned interval surgery
• MMR-D on immunohistochemistry OR MSI-H using any commercially available test
• Patients with treated brain metastases are eligible if follow up brain imaging after CNS directed therapy shows no evidence of progression.
• Eligible for standard of care chemotherapy with immune checkpoint inhibitor per treating investigator with no clinical contraindications

• For the up to 10 patients who are allowed to enroll after C1D1 of standard of care treatments, they need to be on treatment with no clinical evidence of disease progression.

  • Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy.
  • Patients may have received prior hormonal therapy for treatment of endometrial cancer.

  • Patients may not have received prior therapy with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.

    • Except for the up to 10 patients who are allowed to enroll after C1D1 of standard of care treatments (chemotherapy and/or immune checkpoint inhibitors) per protocol.
• Age ≥ 18
• Not Pregnant and Not Nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ctDNA-negative group; Participants in this group will have negative ctDNA test results at 1 year after they start standard treatment. (Negative results indicate that no cancer DNA is detected in their blood.) Participants in this group will decide with their doctor if they want to stop standard maintenance ICI treatment.	Genetic: ctDNA Testing; Patients will undergo ctDNA sampling at the 1-year timepoint using the commercially available Natera SignateraTM test.; Other: Blood draw; at the 1-year timepoint; Other: Surveys; Patients and providers will also complete surveys at various timepoints to evaluate distress, shared decision-making, acceptability and other factors contributing to the decision-making process.; Other: Semi-structured interviews; Will be performed within 6 months of receiving the 1-year clinical ctDNA result. Discussion via telephone or during a standard of care clinical visit (in person or telemedicine) with treating physician or team member within 28 days of clinical 1-year ctDNA result to discuss results with the patient and decide on de-escalation if applicable.
Experimental: ctDNA-positive group; Participants in this group will have positive ctDNA test results at 1 year after they start standard treatment. (Positive results indicate that cancer DNA is detected in their blood.) Participants in this group will continue receiving standard treatment with their doctor.	Genetic: ctDNA Testing; Patients will undergo ctDNA sampling at the 1-year timepoint using the commercially available Natera SignateraTM test.; Other: Blood draw; at the 1-year timepoint; Other: Surveys; Patients and providers will also complete surveys at various timepoints to evaluate distress, shared decision-making, acceptability and other factors contributing to the decision-making process.; Other: Semi-structured interviews; Will be performed within 6 months of receiving the 1-year clinical ctDNA result. Discussion via telephone or during a standard of care clinical visit (in person or telemedicine) with treating physician or team member within 28 days of clinical 1-year ctDNA result to discuss results with the patient and decide on de-escalation if applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
will test the feasibility of ct-DNA	informed de-escalation of standard of care ICI maintenance therapy defined as willingness of patients/providers to stop ICI therapy after 1 year in those with negative ctDNA testing.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Ying Liu, MD, MPH, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Actual): December 8, 2025

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Stage IV; Stage III with residual disease; Recurrent endometrial cancer after adjuvant therapy only; ctDNA Testing; 25-337
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Surveys and Questionnaires; Blood Specimen Collection
• Other Study ID Numbers: 25-337

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

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