An interventional study of Signatera Genome ultra-sensitive ctDNA blood test in Endometrial Cancer, sponsored by Natera, Inc.. Not yet recruiting at 12 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-17.
Sponsored by Natera, Inc. · Not applicable, Interventional, and Treatment
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:
Participants will be asked to:
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:
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.
1,425 studies on the registry are indexed under Endometrial Neoplasms; 473 are open to participants now.
This study's planned enrollment of 1,010 is above the median of 71 across 1,026 interventional studies indexed under Endometrial Neoplasms.
Browse Endometrial Neoplasms studies →Natera, Inc. is the lead sponsor of 36 studies on the registry; 11 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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 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
Stage I patients with endometrioid histology:
Uterine risk factors include:
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
a. FIGO 2009 Stage I with high risk histology i. Defined as serous, clear cell, carcinosarcoma, or mixed histology.
2. Low risk cohort
a. 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
Exclusion Criteria:
Patients are not eligible for the study if they meet any of the following criteria, as assessed by the investigator:
Prior therapy for endometrial cancer (including hormonal therapy, chemotherapy, targeted therapy, immunotherapy)
a. or other hormonal management for endometrial intraepithelial hyperplasia is allowed
Patients with a history of other invasive , with the exception of non-melanoma skin cancer, are excluded if there is any evidence of active malignancy within the last five years.
a. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will be monitored by their study physician and will not receive treatment
Device: Signatera Genome ultra-sensitive ctDNA blood test
Participants will receive standard-of-care vaginal brachytherapy
Device: Signatera Genome ultra-sensitive ctDNA blood test
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.
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.
Time frame: 3 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first
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.
Time frame: From enrollment to Year 3 and enrollment to Year 5
ctDNA Clearance Rate
Estimate the ctDNA clearance rate among high-intermediate risk ctDNA positive participants.
Time frame: From enrollment until first surveillance visit at 12 weeks
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.
Time frame: Up to 5 years from enrollment
Lead time of ctDNA positivity
Examine differences in lead time of ctDNA positivity relative to clinical or radiologic diagnosis of recurrence across different ctDNA dynamic groups (e.g. clearance, persistent negative) among LR, HIR, and HR patients.
Time frame: Up to 5 years from enrollment
Disease-specific recurrence
Determine disease-specific recurrence among high-intermediate risk patients.
Time frame: At 3 years and 5 years.
ctDNA positivity rate
Assess ctDNA positivity rate, defined as proportion of patients, among all HIR, HR, and LR patients with evaluable ctDNA results
Time frame: From randomization to 3 years and 5 years
ctDNA negativity rate
ctDNA negativity rate, defined as proportion of patients with a negative ctDNA, among all HIR, HR, and LR patients with evaluable ctDNA results.
Time frame: From randomization to 3 years and 5 years
ctDNA clearance rate
Assess the ctDNA clearance rate of ctDNA from HIR, HR, and LR participants.
Time frame: From enrollment up to 5 years
ctDNA negative persistence rate
Assess proportion of HIR, HR, and LR participants who remain ctDNA-negative throughout the surveillance period among participants who were ctDNA-negative post-operatively or post-adjuvant treatment.
Time frame: From enrollment to end of treatment and up to 5 years.
Mean Tumor Molecules (MTM)
Assess mean tumor molecules (MTM) presence change over time in HIR, HR, and LR participants.
Time frame: From enrollment to up to 5 years
Variant Allele Frequencies (VAF)
Assess variant allele frequencies (VAF) changes over time in HIR, HR, and LR participants.
Time frame: From enrollment up to 5 years
Cost-effectiveness of ctDNA guided care
Compare the ctDNA cost for High-Risk Intermediate endometrial cancer participants who were randomized to the observation cohort to those that received standard of care (VBT) treatment
Time frame: Up to 5 years from enrollment
Quality of Life Outcomes
Compare Quality of Life (QoL) outcomes between the Observation and Vaginal Brachytherapy (VBT) treatment arms among HIR patients, utilizing the Functional Assessment of Cancer Therapy - Endocrine Symptoms Version 4 (FACT-ES) patient-reported outcome (PRO).
Time frame: Up to 5 years from enrollment
Plan to share: No
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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