[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100619035":3},{"organization":4,"outcomesModule":7,"designInfo":62,"detailedDescription":73,"studyPopulation":65,"armGroups":74,"interventions":86,"overallOfficials":92,"centralContacts":96,"locations":102,"responsibleParty":256,"collaborators":65,"id":258,"slug":65,"hasResults":259,"nctId":260,"briefTitle":261,"officialTitle":262,"acronym":263,"eligibilityCriteria":264,"healthyVolunteers":259,"sex":265,"minAge":266,"maxAge":65,"enrollmentInfo":267,"targetDuration":65,"studyType":270,"phases":271,"briefSummary":273,"conditions":274,"keywords":276,"overallStatus":288,"whyStopped":65,"lastUpdateSubmitDate":289,"lastUpdatePostDateStruct":290,"startDateStruct":293,"completionDateStruct":295,"leadSponsor":297,"locationsCount":298},{"fullName":5,"class":6},"Natera, Inc.","INDUSTRY",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":26},[9],{"measure":10,"description":11,"timeFrame":12},"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.","3 years from randomization to the first occurrence of disease recurrence or death from any cause, whichever occurs first",[14,18,22],{"measure":15,"description":16,"timeFrame":17},"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.","From enrollment to Year 3 and enrollment to Year 5",{"measure":19,"description":20,"timeFrame":21},"ctDNA Clearance Rate","Estimate the ctDNA clearance rate among high-intermediate risk ctDNA positive participants.","From enrollment until first surveillance visit at 12 weeks",{"measure":23,"description":24,"timeFrame":25},"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\u002Fracial groups among high-intermediate risk patients.","Up to 5 years from enrollment",[27,30,34,38,41,45,49,53,56,59],{"measure":28,"description":29,"timeFrame":25},"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.",{"measure":31,"description":32,"timeFrame":33},"Disease-specific recurrence","Determine disease-specific recurrence among high-intermediate risk patients.","At 3 years and 5 years.",{"measure":35,"description":36,"timeFrame":37},"ctDNA positivity rate","Assess ctDNA positivity rate, defined as proportion of patients, among all HIR, HR, and LR patients with evaluable ctDNA results","From randomization to 3 years and 5 years",{"measure":39,"description":40,"timeFrame":37},"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.",{"measure":42,"description":43,"timeFrame":44},"ctDNA clearance rate","Assess the ctDNA clearance rate of ctDNA from HIR, HR, and LR participants.","From enrollment up to 5 years",{"measure":46,"description":47,"timeFrame":48},"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.","From enrollment to end of treatment and up to 5 years.",{"measure":50,"description":51,"timeFrame":52},"Mean Tumor Molecules (MTM)","Assess mean tumor molecules (MTM) presence change over time in HIR, HR, and LR participants.","From enrollment to up to 5 years",{"measure":54,"description":55,"timeFrame":44},"Variant Allele Frequencies (VAF)","Assess variant allele frequencies (VAF) changes over time in HIR, HR, and LR participants.",{"measure":57,"description":58,"timeFrame":25},"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",{"measure":60,"description":61,"timeFrame":25},"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).",{"allocation":63,"interventionModel":64,"interventionModelDescription":65,"primaryPurpose":66,"observationalModel":65,"timePerspective":65,"maskingInfo":67},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":68,"maskingDescription":69,"whoMasked":70},"DOUBLE","Following the initial baseline test, providers in Arm A will be blinded to all subsequent ctDNA results unless ctDNA positive within the first 12 weeks in Arm A (in which case, the provider will be notified and TPC will be initiated).\n\nProviders treating participants in Arm B will remain blinded to all ctDNA results following the initial baseline test. Providers and patients enrolled in the early stage low-risk and high-risk cohorts will be blinded to all ctDNA results (post-operatively, during treatment, and during surveillance).",[71,72],"PARTICIPANT","INVESTIGATOR","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.\n\nFollowing 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:\n\n* Arm A: Observation unless ctDNA positivity within baseline window (\\\u003C12 weeks), with serial ctDNA monitoring.\n* Arm B: Vaginal brachytherapy (VBT) with serial ctDNA monitoring.\n\nFollowing 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\u002For chemotherapy. Providers and patients will be unblinded to the initial ctDNA result and blinded to ctDNA results thereafter.\n\nThe 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\u002For chemotherapy, and during surveillance. Providers and patients will be blinded to ctDNA results during the post-operative, TPC and surveillance period.",[75,81],{"label":76,"type":77,"description":78,"interventionNames":79},"Observation","OTHER","Participants will be monitored by their study physician and will not receive treatment",[80],"Device: Signatera Genome ultra-sensitive ctDNA blood test",{"label":82,"type":83,"description":84,"interventionNames":85},"Vaginal Brachytherapy (VBT)","ACTIVE_COMPARATOR","Participants will receive standard-of-care vaginal brachytherapy",[80],[87],{"type":88,"name":89,"description":90,"armGroupLabels":91,"otherNames":65},"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.",[76,82],[93],{"name":94,"affiliation":5,"role":95},"Adam ElNaggar, MD","STUDY_DIRECTOR",[97],{"name":98,"role":99,"phone":100,"phoneExt":65,"email":101},"Brooke Cormane, MBS","CONTACT","844-778-4700","bcormane@natera.com",[103,120,133,145,158,171,184,196,209,221,234,246],{"facility":104,"status":65,"city":105,"state":106,"zip":107,"country":108,"countryCode":109,"cosmosGeoPoint":110,"geoPoint":115,"contacts":116},"University of Alabama at Birmingham Hospital","Birmingham","Alabama","35294","United States","US",{"type":111,"coordinates":112},"Point",[113,114],-86.80249,33.52066,{"lat":114,"lon":113},[117],{"name":118,"role":119,"phone":65,"phoneExt":65,"email":65},"Michael Toboni, MD","PRINCIPAL_INVESTIGATOR",{"facility":121,"status":65,"city":122,"state":123,"zip":124,"country":108,"countryCode":109,"cosmosGeoPoint":125,"geoPoint":129,"contacts":130},"University of California, San Diego","La Jolla","California","92093",{"type":111,"coordinates":126},[127,128],-117.2742,32.84727,{"lat":128,"lon":127},[131],{"name":132,"role":119,"phone":65,"phoneExt":65,"email":65},"Ramez Eskander, MD",{"facility":134,"status":65,"city":135,"state":123,"zip":136,"country":108,"countryCode":109,"cosmosGeoPoint":137,"geoPoint":141,"contacts":142},"University of California, Los Angeles","Los Angeles","90095",{"type":111,"coordinates":138},[139,140],-118.24368,34.05223,{"lat":140,"lon":139},[143],{"name":144,"role":119,"phone":65,"phoneExt":65,"email":65},"Dana Chase, MD",{"facility":146,"status":65,"city":147,"state":148,"zip":149,"country":108,"countryCode":109,"cosmosGeoPoint":150,"geoPoint":154,"contacts":155},"University of Miami","Miami","Florida","33146",{"type":111,"coordinates":151},[152,153],-80.19366,25.77427,{"lat":153,"lon":152},[156],{"name":157,"role":119,"phone":65,"phoneExt":65,"email":65},"Abdulrahman Sinno, MD",{"facility":159,"status":65,"city":160,"state":161,"zip":162,"country":108,"countryCode":109,"cosmosGeoPoint":163,"geoPoint":167,"contacts":168},"University of Chicago","Chicago","Illinois","60637",{"type":111,"coordinates":164},[165,166],-87.65005,41.85003,{"lat":166,"lon":165},[169],{"name":170,"role":119,"phone":65,"phoneExt":65,"email":65},"Katherine Kurnit, MD",{"facility":172,"status":65,"city":173,"state":174,"zip":175,"country":108,"countryCode":109,"cosmosGeoPoint":176,"geoPoint":180,"contacts":181},"University of Minnesota","Minneapolis","Minnesota","55455",{"type":111,"coordinates":177},[178,179],-93.26384,44.97997,{"lat":179,"lon":178},[182],{"name":183,"role":119,"phone":65,"phoneExt":65,"email":65},"Melissa Geller, MD",{"facility":185,"status":65,"city":186,"state":186,"zip":187,"country":108,"countryCode":109,"cosmosGeoPoint":188,"geoPoint":192,"contacts":193},"New York University","New York","10016",{"type":111,"coordinates":189},[190,191],-74.00597,40.71427,{"lat":191,"lon":190},[194],{"name":195,"role":119,"phone":65,"phoneExt":65,"email":65},"Bhavana Pothuri, MD",{"facility":197,"status":65,"city":198,"state":199,"zip":200,"country":108,"countryCode":109,"cosmosGeoPoint":201,"geoPoint":205,"contacts":206},"Atrium Health Levine Cancer","Charlotte","North Carolina","28204",{"type":111,"coordinates":202},[203,204],-80.84313,35.22709,{"lat":204,"lon":203},[207],{"name":208,"role":119,"phone":65,"phoneExt":65,"email":65},"Allison Puechl, MD",{"facility":210,"status":65,"city":211,"state":199,"zip":212,"country":108,"countryCode":109,"cosmosGeoPoint":213,"geoPoint":217,"contacts":218},"Duke University","Durham","27708",{"type":111,"coordinates":214},[215,216],-78.89862,35.99403,{"lat":216,"lon":215},[219],{"name":220,"role":119,"phone":65,"phoneExt":65,"email":65},"Angeles Secord, MD",{"facility":222,"status":65,"city":223,"state":224,"zip":225,"country":108,"countryCode":109,"cosmosGeoPoint":226,"geoPoint":230,"contacts":231},"Cleveland Clinic","Cleveland","Ohio","44106",{"type":111,"coordinates":227},[228,229],-81.69541,41.4995,{"lat":229,"lon":228},[232],{"name":233,"role":119,"phone":65,"phoneExt":65,"email":65},"Kevin Elias, MD",{"facility":235,"status":65,"city":236,"state":224,"zip":237,"country":108,"countryCode":109,"cosmosGeoPoint":238,"geoPoint":242,"contacts":243},"Ohio State University Wexner Medical Center","Columbus","43210",{"type":111,"coordinates":239},[240,241],-82.99879,39.96118,{"lat":241,"lon":240},[244],{"name":245,"role":119,"phone":65,"phoneExt":65,"email":65},"Floor Backes, MD",{"facility":247,"status":65,"city":248,"state":249,"zip":250,"country":108,"countryCode":109,"cosmosGeoPoint":251,"geoPoint":255,"contacts":65},"Allegheny Health","Pittsburgh","Pennsylvania","15224",{"type":111,"coordinates":252},[253,254],-79.99589,40.44062,{"lat":254,"lon":253},{"type":257,"investigatorFullName":65,"investigatorTitle":65,"investigatorAffiliation":65,"oldNameTitle":65,"oldOrganization":65},"SPONSOR","100619035",false,"NCT07339384","Signatera Assessment in Early-Stage Endometrial Cancer","Circulating Tumor DNA Assessment in Early-Stage Endometrial Cancer (SIGNAL-EMC 101)","SIGNAL-EMC 101","Inclusion Criteria:\n\nGeneral 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:\n\n1\\. Signed and dated informed consent form (ICF) obtained prior to any trial-specific enrollment procedure.\n\n2\\. Patient is ≥ 18 years-old at the time of ICF signature. 3. Able to submit sufficient residual tissue obtained per standard of care procedures.\n\nHIR 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:\n\n1. FIGO 2009 Stage I after hysterectomy and lymph node assessment by bilateral pelvic lymphadenectomy or SLND\n\n   1. If para-aortic lymph nodes are not pathologically assessed, documentation of surgical assessment or imaging is recommended.\n2. Stage I patients with endometrioid histology:\n\n   1. Age 70 years or older with one uterine risk factor,\n   2. Age 50-69 years with two risk factors,\n   3. Age 18 - 49 years with three risk factors.\n\nUterine risk factors include:\n\n* Grade 2 or 3 tumor.\n* Outer half depth of invasion.\n* Lymphovascular invasion. Note: peritoneal cytology must be negative if performed.\n\nPatients 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:\n\n1\\. High risk cohort\n\na. FIGO 2009 Stage I with high risk histology i. Defined as serous, clear cell, carcinosarcoma, or mixed histology.\n\n1. Negative peritoneal cytology, where performed (recommended)\n2. If para-aortic lymph nodes are not pathologically assessed, imaging is required b. FIGO 2009 Stage II Endometrioid\n\n2\\. Low risk cohort\n\na. 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\n\nExclusion Criteria:\n\nPatients are not eligible for the study if they meet any of the following criteria, as assessed by the investigator:\n\n1. Undifferentiated or dedifferentiated histology\n2. Uterine sarcoma\n3. Prior pelvic radiation therapy\n4. Positive pelvic washings\n5. Pelvic lymph node assessment was not performed\n6. Isolated Tumor Cells (ITC) identified in the lymph node(s)\n7. Prior therapy for endometrial cancer (including hormonal therapy, chemotherapy, targeted therapy, immunotherapy)\n\n   a. Contraceptives or other hormonal management for endometrial intraepithelial hyperplasia is allowed\n8. 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.\n\n   a. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.\n9. Patients with a history of serious comorbid illness or uncontrolled illnesses that would preclude protocol therapy.\n10. Patients with a history of myocardial infarction, unstable angina, or uncontrolled arrhythmia within 3 months from enrollment.\n11. Previous diagnosis of Crohn's disease or ulcerative colitis.\n12. Patient is currently receiving, or plans to receive, commercial ctDNA\u002FMRD assay for disease monitoring, excluding Signatera. Patients must agree to forego testing with assays other than Signatera Genome upon enrollment until end of study.","FEMALE","18 Years",{"count":268,"type":269},1010,"ESTIMATED","INTERVENTIONAL",[272],"NA","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:\n\n• 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.\n\nParticipants will be asked to:\n\n* Receive serial ctDNA testing\n* Visit their study doctor per their standard of care visits about every 3 months for 2 years\n* Answer a questionnaire about their well-being",[275],"Endometrial Cancer",[277,275,278,279,280,281,282,283,284,285,286,287],"ctDNA","circulating tumor","Signatera","Molecular Residual Disease","MRD","biomarker-guided therapy","Vaginal Brachytherapy","VBT","High-Intermediate Risk Endometrial Cancer","Adjuvant Therapy","Tumor-informed assay","NOT_YET_RECRUITING","2026-06-15",{"date":291,"type":292},"2026-06-17","ACTUAL",{"date":294,"type":269},"2026-10",{"date":296,"type":269},"2034-10",{"name":5,"class":6},12]