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Endometrial CancerSIGNAL-EMC 101NCT07339384

Signatera Assessment in Early-Stage Endometrial Cancer

A study testing Signatera Genome ultra-sensitive ctDNA blood test in people with Endometrial Cancer, run by Natera, Inc. at 12 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this clinical trial is to assess if circulating tumor DNA can guide adjuvant selection in high-intermediate risk early-stage endometrial cancer. The main question it aims to answer is: To evaluate if 3-year recurrence-free survival among women with Stage I, high-intermediate risk endometrial cancer who are… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Endometrial Cancer
What is being tested?
Signatera Genome ultra-sensitive ctDNA blood test
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,010 participants
Where
12 sitesUnited States
Study dates
Oct 2026to Oct 2034
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General inclusion criteria includes the following selection criteria to be eligible for inclusion in any aspect of the study. Eligibility will be assessed by the investigator:
  • 1. Signed and dated informed consent form (ICF) obtained prior to any trial-specific enrollment procedure.
  • 2. Patient is ≥ 18 years-old at the time of ICF signature. 3. Able to submit sufficient residual tissue obtained per standard of care procedures.
  • HIR patients must meet all the following selection criteria to be eligible for the randomization cohort in the study. Eligibility will be assessed by the investigator:
  • FIGO 2009 Stage I after hysterectomy and lymph node assessment by bilateral pelvic lymphadenectomy or SLND
  • If para-aortic lymph nodes are not pathologically assessed, documentation of surgical assessment or imaging is recommended.
Show all 21Show fewer
  • Stage I patients with endometrioid histology:
  • Age 70 years or older with one uterine risk factor,
  • Age 50-69 years with two risk factors,
  • Age 18 - 49 years with three risk factors.
  • Uterine risk factors include:
  • Grade 2 or 3 tumor.
  • Outer half depth of invasion.
  • Lymphovascular invasion. Note: peritoneal cytology must be negative if performed.
  • Patients must meet all the following selection criteria to be eligible for the observation arms of the study. Eligibility will be assessed by the investigator following hysterectomy and lymph node assessment by bilateral pelvic and para-aortic lymphadenectomy or SLND:
  • 1. High risk cohort
  • FIGO 2009 Stage I with high risk histology i. Defined as serous, clear cell, carcinosarcoma, or mixed histology.
  • Negative peritoneal cytology, where performed (recommended)
  • If para-aortic lymph nodes are not pathologically assessed, imaging is required b. FIGO 2009 Stage II Endometrioid
  • 2. Low risk cohort
  • FIGO 2009 Stage I patients at low risk of recurrence i. Endometriod histology ii. Absent uterine risk factors, or present but insufficient to meet HIR criteria

Who cannot join

  • Patients are not eligible for the study if they meet any of the following criteria, as assessed by the investigator:
  • Undifferentiated or dedifferentiated histology
  • Uterine sarcoma
  • Prior pelvic radiation therapy
  • Positive pelvic washings
  • Pelvic lymph node assessment was not performed
Show all 15Show fewer
  • Isolated Tumor Cells (ITC) identified in the lymph node(s)
  • Prior therapy for endometrial cancer (including hormonal therapy, chemotherapy, targeted therapy, immunotherapy)
  • Contraceptives or other hormonal management for endometrial intraepithelial hyperplasia is allowed
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of active malignancy within the last five years.
  • Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
  • Patients with a history of serious comorbid illness or uncontrolled illnesses that would preclude protocol therapy.
  • Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment.
  • Previous diagnosis of Crohn's disease or ulcerative colitis.
  • Patient is currently receiving, or plans to receive, commercial ctDNA/MRD assay for disease monitoring, excluding Signatera. Patients must agree to forego testing with assays other than Signatera Genome upon enrollment until end of study.

Trial locations and contacts

12 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Brooke Cormane, MBS contact

844-778-4700

bcormane@natera.com

12 sites in 1 country

United States12 sites

  • University of Alabama at Birmingham Hospital

    Birmingham, Alabama, 35294

    Michael Toboni, MD

  • Atrium Health Levine Cancer

    Charlotte, North Carolina, 28204

    Allison Puechl, MD

  • University of Chicago

    Chicago, Illinois, 60637

    Katherine Kurnit, MD

  • Cleveland Clinic

    Cleveland, Ohio, 44106

    Kevin Elias, MD

  • Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

    Floor Backes, MD

  • Duke University

    Durham, North Carolina, 27708

    Angeles Secord, MD

  • University of California, San Diego

    La Jolla, California, 92093

    Ramez Eskander, MD

  • University of California, Los Angeles

    Los Angeles, California, 90095

    Dana Chase, MD

  • University of Miami

    Miami, Florida, 33146

    Abdulrahman Sinno, MD

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    Melissa Geller, MD

  • New York University

    New York, New York, 10016

    Bhavana Pothuri, MD

  • Allegheny Health

    Pittsburgh, Pennsylvania, 15224

Other trials in United States

About this study

Official title: Circulating Tumor DNA Assessment in Early-Stage Endometrial Cancer (SIGNAL-EMC 101)

The goal of this clinical trial is to assess if circulating tumor DNA can guide adjuvant selection in high-intermediate risk early-stage endometrial cancer. The main question it aims to answer is:

  • To evaluate if 3-year recurrence-free survival among women with Stage I, high-intermediate risk endometrial cancer who are ctDNA negative after receiving ctDNA-guided observation is non-inferior to adjuvant vaginal brachytherapy (an internal radiation therapy) Researchers will compare high-risk intermediate ctDNA negative participants who are observed to those who receive vaginal brachytherapy to see if they have similar outcomes.
Read more

Participants will be asked to:

  • Receive serial ctDNA testing
  • Visit their study doctor per their standard of care visits about every 3 months for 2 years
  • Answer a questionnaire about their well-being
Read the detailed description

This includes a randomized, multi-center, non-inferiority trial for a biomarker-defined subgroup, alongside two parallel, non-randomized exploratory cohorts. The study utilizes a biomarker-stratified design to formally test a treatment de-escalation strategy in patients with HIR endometrial cancer.

Following surgery, patients in the HIR cohort will be stratified based on post-operative circulating tumor DNA (ctDNA) status, as determined by the Signatera Genome assay. ctDNA-negative HIR Patients, based on the first valid post-operative ctDNA result within the baseline window, will be randomized (1:1) to either:

  • Arm A: Observation unless ctDNA positivity within baseline window (<12 weeks), with serial ctDNA monitoring.
  • Arm B: Vaginal brachytherapy (VBT) with serial ctDNA monitoring.

Following the initial baseline test, providers will be blinded to subsequent ctDNA results unless ctDNA positive within the first 12 weeks in Arm A [in which case, the provider will be notified and treatment of physician's choice (TPC) will be initiated. Initiation of TPC following ctDNA conversion is considered part of the ctDNA-guided treatment strategy, not a protocol deviation or cross-over, and such patients remain in the intent-to-treat population in Arm A]. Providers treating patients in Arm B will remain blinded to all ctDNA results after randomization. Post-operative ctDNA-Positive HIR patients will not be randomized and will continue serial testing while receiving TPC, which may include observation, radiation and/or chemotherapy. Providers and patients will be unblinded to the initial ctDNA result and blinded to ctDNA results thereafter.

The study will also include early stage low-risk (LR) and high-risk (HR) cohorts. Patients in these cohorts will not be randomized. They will continue serial ctDNA testing while receiving TPC, which may include observation, radiation and/or chemotherapy, and during surveillance. Providers and patients will be blinded to ctDNA results during the post-operative, TPC and surveillance period.

Being tested
Signatera Genome ultra-sensitive ctDNA blood test
Keywords
ctDNA, Endometrial Cancer, circulating tumor, Signatera, Molecular Residual Disease, MRD, biomarker-guided therapy, Vaginal Brachytherapy, VBT, High-Intermediate Risk Endometrial Cancer, Adjuvant Therapy, Tumor-informed assay
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Signatera Genome ultra-sensitive ctDNA blood testDevice

    Signatera Genome is intended for use as a post-surgical risk stratification tool for patients with early-stage HIR endometrial cancer. The test is used to identify patients with no evidence of MRD following definitive surgery.

Study groups in NCT07339384
Study groupRoleWhat they receive
ObservationOtherParticipants will be monitored by their study physician and will not receive treatment
Receives: Device: Signatera Genome ultra-sensitive ctDNA blood test
Vaginal Brachytherapy (VBT)Active comparatorParticipants will receive standard-of-care vaginal brachytherapy
Receives: Device: Signatera Genome ultra-sensitive ctDNA blood test

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrence Free Survival (RFS)

    The primary objective of this study is to evaluate if recurrence free survival (RFS) is non-inferior among women with stage I high-intermediate risk endometrial cancer who are ctDNA-negative after surgery and managed with ctDNA-guided observation versus adjuvant VBT.

    Measured: 3 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first

Secondary outcomes (3)

  1. Overall Survial

    Comparison of overall survival (OS) among all high-intermediate risk (HIR) patients and recurrence free survival (RFS) across treatment groups and assess whether ctDNA-guided de-escalation group is non-inferior to adjuvant VBT.

    Measured: From enrollment to Year 3 and enrollment to Year 5

  2. ctDNA Clearance Rate

    Estimate the ctDNA clearance rate among high-intermediate risk ctDNA positive participants.

    Measured: From enrollment until first surveillance visit at 12 weeks

  3. Clinicopathologic and Molecular Risk Factors

    Assess the primary and secondary objectives by clinicopathologic and molecular (e.g. POLE, MMR-D, p53 aberrant, p53 wild type) risk factors, and ethnic/racial groups among high-intermediate risk patients.

    Measured: Up to 5 years from enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2026
  2. Study startOct 2026 (estimated)
  3. Primary completionOct 2034 (estimated)
  4. Study completionOct 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,010 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07339384
Sponsor's protocol ID
25-102-NCP
Acronym
SIGNAL-EMC 101
Status last verified
Jun 2026
First submitted
30 Dec 2025
Last updated
17 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Firth, D. (1993). Bias reduction of maximum likelihood estimates. Biometrika, 80(1), 27-38

  • Mahdi H, Elshaikh MA, DeBenardo R, Munkarah A, Isrow D, Singh S, Waggoner S, Ali-Fehmi R, Morris RT, Harding J, Moslemi-Kebria M. Impact of adjuvant chemotherapy and pelvic radiation on pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multi-institution study. Gynecol Oncol. 2015 May;137(2):239-44. doi: 10.1016/j.ygyno.2015.01.544. Epub 2015 Jan 29.

    PubMed 25641568

  • Creutzberg CL, van Putten WL, Warlam-Rodenhuis CC, van den Bergh AC, de Winter KA, Koper PC, Lybeert ML, Slot A, Lutgens LC, Stenfert Kroese MC, Beerman H, van Lent M; postoperative Radiation Therapy in Endometrial Carcinoma Trial. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004 Apr 1;22(7):1234-41. doi: 10.1200/JCO.2004.08.159.

    PubMed 15051771

  • Hamilton CA, Cheung MK, Osann K, Chen L, Teng NN, Longacre TA, Powell MA, Hendrickson MR, Kapp DS, Chan JK. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer. 2006 Mar 13;94(5):642-6. doi: 10.1038/sj.bjc.6603012.

    PubMed 16495918

  • Siegenthaler F, Lindemann K, Epstein E, Rau TT, Nastic D, Ghaderi M, Rydberg F, Mueller MD, Carlson J, Imboden S. Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification. Gynecol Oncol. 2022 May;165(2):230-238. doi: 10.1016/j.ygyno.2022.02.024. Epub 2022 Mar 8.

    PubMed 35277281

  • Feng W, Jia N, Jiao H, Chen J, Chen Y, Zhang Y, Zhu M, Zhu C, Shen L, Long W. Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer. J Transl Med. 2021 Feb 3;19(1):51. doi: 10.1186/s12967-021-02722-8.

    PubMed 33536036

  • Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, Oaknin A. Endometrial cancer. Nat Rev Dis Primers. 2021 Dec 9;7(1):88. doi: 10.1038/s41572-021-00324-8.

    PubMed 34887451

  • Kalampokas E, Giannis G, Kalampokas T, Papathanasiou AA, Mitsopoulou D, Tsironi E, Triantafyllidou O, Gurumurthy M, Parkin DE, Cairns M, Vlahos NF. Current Approaches to the Management of Patients with Endometrial Cancer. Cancers (Basel). 2022 Sep 16;14(18):4500. doi: 10.3390/cancers14184500.

    PubMed 36139659

  • Clarke MA, Devesa SS, Harvey SV, Wentzensen N. Hysterectomy-Corrected Uterine Corpus Cancer Incidence Trends and Differences in Relative Survival Reveal Racial Disparities and Rising Rates of Nonendometrioid Cancers. J Clin Oncol. 2019 Aug 1;37(22):1895-1908. doi: 10.1200/JCO.19.00151. Epub 2019 May 22.

    PubMed 31116674

  • Giaquinto AN, Broaddus RR, Jemal A, Siegel RL. The Changing Landscape of Gynecologic Cancer Mortality in the United States. Obstet Gynecol. 2022 Mar 1;139(3):440-442. doi: 10.1097/AOG.0000000000004676.

    PubMed 35115431

  • https://seer.cancer.gov/csr/1975_2018/

  • Sohaib SA, Houghton SL, Meroni R, Rockall AG, Blake P, Reznek RH. Recurrent endometrial cancer: patterns of recurrent disease and assessment of prognosis. Clin Radiol. 2007 Jan;62(1):28-34; discussion 35-6. doi: 10.1016/j.crad.2006.06.015.

    PubMed 17145260

  • Howlader N, N.A., Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds), SEER Cancer Statistics Review, 1975-2017. National Cancer Institute. Bethesda, MD

  • Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.

    PubMed 39817679

  • van den Heerik ASVM, Horeweg N, Creutzberg CL, Nout RA. Vaginal brachytherapy management of stage I and II endometrial cancer. Int J Gynecol Cancer. 2022 Mar;32(3):304-310. doi: 10.1136/ijgc-2021-002493.

    PubMed 35256416

Questions about this trial

What is this clinical trial studying?

A study testing Signatera Genome ultra-sensitive ctDNA blood test in people with Endometrial Cancer, run by Natera, Inc. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Brooke Cormane, MBS (844-778-4700, bcormane@natera.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrence Free Survival (RFS) (time frame: 3 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07339384, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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