What this study is
The purpose of this study is to evaluate the efficacy and safety of ctDNA-guided initiation of CDK4/6 inhibitor therapy using the Signatera™ Designed on Genome test (referred to as "Signatera Genome") in participants with intermediate-risk HR+/HER2- early-stage breast cancer. Based on ctDNA test results, participants will either start CDK4/6 inhibitor therapy in addition to hormone therapy or continue hormone therapy with ongoing ctDNA surveillance. This study will compare outcomes to historical controls from the NataLEE trial to determine whether ctDNA-guided timing maintains efficacy while reducing unnecessary treatment. Participants will be followed for up to 9 years with regular blood draws, hormone therapy, imaging as needed, and quality-of-life assessments.
What's being tested
- ctDNA-Guided Treatment Strategy
Intervention · DEVICE
Circulating tumor DNA testing using Signatera Genome assay is performed every 3 months for up to 4 years to guide timing of CDK4/6 inhibitor initiation. Participants with positive ctDNA results initiate CDK4/6 inhibitor therapy (ribociclib or abemaciclib) plus standard endocrine therapy for a minimum of 2 years. Participants with negative ctDNA results continue endocrine therapy alone with ongoing surveillance. CDK4/6 inhibitor selection and endocrine therapy regimen per the physician's choice following standard-of-care guidelines.
Study details
- Official title
- SIgnatera-Guided Initiation of Adjuvant CDK4/6 Inhibitor in Intermediate Risk HR+ HER2- Breast Cancer
- Sponsor
- Natera, Inc.
- Conditions
- Breast Neoplasms · Carcinoma, Ductal, Breast · Receptors, Estrogen (for ER-positive Requirement)
- Enrolling
- 725 people
- Starts
- 2026-05-08
- Est. completion
- 2037-12-30
- Design
- Open-label, single group
- Record
- View on ClinicalTrials.gov ↗
Who can join
Age 18 Years and overSex ALLHealthy volunteers Not acceptedYou may qualify if
- Signed and dated Informed Consent Form (ICF) obtained prior to any trial-specific screening procedure.
- Patient is ≥ 18 years-old at the time of ICF signature.
- Patient is female with known menopausal status at the time of initiation of adjuvant endocrine therapy (ET), or male.
- Patient with histologically confirmed unilateral and unifocal primary invasive adenocarcinoma of the breast prior to initiating adjuvant chemotherapy, if indicated, or within 6 months of initiating adjuvant endocrine therapy if chemotherapy is not indicated. Patients who receive neoadjuvant endocrine therapy or chemotherapy are allowed to enroll.
- Patient has breast cancer that is positive for ER and/or PR according to the local laboratory as determined on the most recently analyzed tissue sample.
- Patient has HER2-negative breast cancer defined as a negative in situ hybridization test (FISH, CISH, or SISH) or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (ISH) test is required to confirm the HER2-negative status.
- Patient has available archival tumor tissue from the diagnostic biopsy or surgical specimen, for submission to a central laboratory for Signatera testing (unless Signatera Genome clinical testing has already been performed).
- Patient after surgical resection where tumor was removed completely (i.e., negative microscopic margins on final pathology) and have Anatomic Stage II that is eligible for adjuvant CDK4/6 inhibitors. The criteria to be eligible for adjuvant CDK4/6 inhibitors include N1, or N0 with T3 or T2 with either G3, or G2 with Ki67 greater or equal to 20% or high genomic risk score. Notes:; Patients who received neoadjuvant treatment must meet the criteria for stage, grade, Ki67 in any presurgical staging/sample and/or in the surgical specimen.; Categorization into the AJCC 8th edition Anatomic Stage Groups requires determination of the T, N and M categories. ALND can be omitted.
- Patient has no contraindication to adjuvant ET and is planned to be treated with ET for 5 years (since enrollment date) or more.
- Provider and patient must be agreeable to initiate CDK4/6 inhibitors only upon ctDNA detection.
- Patient may have received up to 6 months of standard adjuvant ET at the time of enrollment and any amount of neoadjuvant endocrine therapy.
- Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Patient must not have a clinical contraindication to ribociclib or abemaciclib.
- Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
- Women of childbearing potential (CBP) must have a confirmed negative serum pregnancy test within 14 days prior to enrollment.
- Women of reproductive potential should be advised of the potential risk of CDK4/6 inhibitors to a fetus, and use effective contraception during CDK 4/6 inhibitor therapy.
You can't join if
- Patient has had prior exposure to a CDK4/6 inhibitor.
- Patient is concurrently using hormone replacement therapy.
- Patient with a known contraindication or hypersensitivity to ribociclib or abemaciclib as per the FDA indication label.
- Patients with a multicentric and/or multifocal and synchronous contralateral breast cancer are ineligible.
- Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
- Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 5 years before ICF signatureExcept: Note: Patients with prior or concurrent in situ malignancies are eligible provided that adequate curative treatment is completed prior to enrollment.
- Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic antibacterial therapy, etc.) or limit life expectancy to ≤5 years.
- Patient participated in another interventional study and received treatment with an investigational product (or used an investigational device) within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
Sign in and we'll check these against your records.Full criteria on ClinicalTrials.gov ↗
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Study locations (50)
50 openMayo Clinic Arizona
Phoenix, Arizona, United States
- Clinical Trials Referral Office · Contact855-776-0015mayocliniccancerstudies@mayo.edu
- Shakeela Bahadur, MD · Principal investigator
Not yet recruitingHonor Health Research Institute
Scottsdale, Arizona, United States
- Nathan Solod · Contact480-295-9344nsolod@honorhealth.com
- Abhimanyu Ghose, MD · Principal investigator
- Wishwdeep Dhillon, MD · Principal investigator
Not yet recruitingUniversity of Arizona Cancer Center
Tucson, Arizona, United States
- Lizeth Evangelista · Contact520-694-2873levangelista@arizona.edu
- Sima Ehsani, MD · Principal investigator
Not yet recruitingMarin Cancer Care
Greenbrae, California, United States
- Jaime Chung · Contact415-925-5040jchang@marincancercare.com
- Cyrus Mazidi, MD · Principal investigator
RecruitingLoma Linda University
Loma Linda, California, United States
- Gayathri Nagaraj, MD · Principal investigator
Not yet recruitingCancer and Blood Research Center
Los Alamitos, California, United States
- John Wong · Principal investigator
Not yet recruitingUCLA David Geffen School of Medicine
Santa Monica, California, United States
- Ruth Gonzalez · Contact424-320-1756Rngonzalez@mednet.ucla.edu
- Marla Lipsyc-Sharf, MD · Principal investigator
Not yet recruitingStockton Hematology Oncology Medical Group
Stockton, California, United States
- Lakshmi Nilyat · Contact209-466-2626lnilyat@shomg.net
- Ajithkumar Puthillath, MD · Principal investigator
RecruitingKaiser Permanente NorCal
Vallejo, California, United States
- Jennifer Suga, MD · Principal investigator
Not yet recruitingIntermountain Health
Grand Junction, Colorado, United States
- Heidi Kaiser · Contact970-298-6576heidi.kaiser@imail.org
- Alicia Swink · Principal investigator
Not yet recruitingHartford Healthcare Institute
Hartford, Connecticut, United States
- Richard Zelkowitz, MD · Principal investigator
Not yet recruitingYale Cancer Center
New Haven, Connecticut, United States
- Carl Brown · Contact475-241-1065carl.brown@yale.edu
- Lajos Pusztai, MD · Principal investigator
Not yet recruitingBaptist MD Anderson
Jacksonville, Florida, United States
- CTOInterest@bmcjax.com · Contact
- Dayra Avila-Lima, MD · Principal investigator
RecruitingMayo Clinic Florida
Jacksonville, Florida, United States
- Mayo Clinic Comprehensive Cancer Center · Contact904-953-2000CANCERCTR@mayo.edu
- Pooja Advani, MD · Principal investigator
Not yet recruitingJupiter Medical Cancer
Jupiter, Florida, United States
- Nancy Nahmias · Contact561-263-5791Nancy.Nahmias@jupitermed.com
- Danielle Krol, MD · Principal investigator
RecruitingWerheim Cancer Institute
Miami, Florida, United States
- Amy Starosciak, PhD. · Contact786-527-9546AmySt@BaptistHealth.net
- Reshma Mahtani, DO · Principal investigator
Not yet recruitingOcala Oncology
Ocala, Florida, United States
- Snjit Nirmalanandhan · Contact352-547-1958Sanjit.Nirmalanandhan@usoncology.com
- Rama Balaraman, MD · Principal investigator
RecruitingNorthwestern University
Chicago, Illinois, United States
- Nicole Grzywacz · Contact312-695-1310nicole.grzywacz@northwestern.edu
- William Gradishar, MD · Principal investigator
Not yet recruitingNorthwest Cancer Center
Dyer, Indiana, United States
- Mariela Abad · ContactMariela.Abad@usoncology.com
- Shruti Singh, MD · Principal investigator
RecruitingIndiana University
Indianapolis, Indiana, United States
- Bryan Schneider · Principal investigator
Not yet recruitingWillis Knighton Cancer Center
Shreveport, Louisiana, United States
- Prakash Peddi, MD · Principal investigator
Not yet recruitingNew England Cancer Specialists
Westbrook, Maine, United States
- Chiara Battelli, MD · Contact207-303-3300research@newecs.org
- Chiara Battelli, MD · Principal investigator
RecruitingMassachusetts General Hospital
Boston, Massachusetts, United States
- Arielle Medford · Principal investigator
Not yet recruitingKarmanos Cancer Center - Wayne State University
Detroit, Michigan, United States
- Allison Wolgast · Contact
- Jailan Elayoubi · Principal investigator
Not yet recruitingCancer & Hematology Centers
Grand Rapids, Michigan, United States
- Maci DeBoar · Contact616-954-5550 ext. 1925mdeboer@thechc.com
- Haritha Reddy · Principal investigator
RecruitingMunson Medical Center Cowell Family Cancer Center
Traverse City, Michigan, United States
- Brook Wright · Contact231-213-0584CFCC-CancerResearch@mhc.net
- Yelena Kier, DO · Principal investigator
RecruitingMayo Clinic
Rochester, Minnesota, United States
- Clinical Trials Referral Office · Contact855-776-0015
- Karthik Giridhar, MD · Principal investigator
Not yet recruitingMercy Health - Sindelar Cancer Center
St Louis, Missouri, United States
- Danielle Werle · Contact314-525-6042Danielle.Werle@Mercy.Net
- Yifan Tu, MD · Principal investigator
Not yet recruitingMercy Health - Pratt Cancer Center
St Louis, Missouri, United States
- Andrea Llewellyn · Contact314-251-6445andrea.llewellyn@Mercy.Net
- Bethany Sleckman, MD · Principal investigator
Not yet recruitingCooper Health
Camden, New Jersey, United States
- Kamel Abou-Hussein, MD · Principal investigator
Not yet recruitingRutgers
New Brunswick, New Jersey, United States
- Stephanie Farias · Contact
- Mridula George, MD · Principal investigator
Not yet recruitingNew Mexico Oncology & Hematology Consultants
Albuquerque, New Mexico, United States
- Sofia Palacio, MD · Contact505-842-8171research@nmohc.com
- Katherine Sanchez · Principal investigator
RecruitingNew York Cancer and Blood Specialists
Babylon, New York, United States
- Research Recruitment · Contactresearchrecruitment@nycancer.com
- Richard Zuniga · Principal investigator
RecruitingNYU Langone Health
New York, New York, United States
- Nancy Chan · Principal investigator
Not yet recruitingUniversity of Rochester (URMC)
Rochester, New York, United States
- Susan Dent, MD · Contact585-275-4401Susan_Dent@URMC.Rochester.edu
- Susan Dent · Principal investigator
Not yet recruitingStony Brook Cancer Center
Stony Brook, New York, United States
- Alison Stopeck · Principal investigator
Not yet recruitingAtrium Levine Cancer Institute
Charlotte, North Carolina, United States
- Arielle Heeke, MD · Principal investigator
Not yet recruitingCleveland Clinic
Cleveland, Ohio, United States
- Cancer Answer Line · Contact216-444-7923Canceranswer@ccf.org
- Azka Ali · Principal investigator
Not yet recruitingAllegheny (AHN)
Pittsburgh, Pennsylvania, United States
- AHN Clinical Trial Contact · Contact412-325-5700clinicaltrials@ahn.org
- Joseph Liput, MD · Principal investigator
Not yet recruitingSanford Health
Sioux Falls, South Dakota, United States
- Allison Watson, MD · Principal investigator
Not yet recruitingWest Cancer Center
Germantown, Tennessee, United States
- Karen Axley · Contact
- Gary Tian, MD · Principal investigator
Not yet recruitingVanderbilt
Nashville, Tennessee, United States
- Brent Rexer, MD · Principal investigator
Not yet recruitingHouston Methodist Hospital
Houston, Texas, United States
- Akshjot Puri, MD · Principal investigator
Not yet recruitingOncology Consultants
Houston, Texas, United States
- Julio Peguero · Contact713-600-0900Jpeguero@oncologyconsultants.com
- Roberto Alvarez, MD · Principal investigator
Not yet recruitingInova
Fairfax, Virginia, United States
- Takada Harris · Contact571-472-4724takada.harris@inova.org
- Melissa Yacur · Principal investigator
Not yet recruitingNorthwest Medical Specialties, PLLC
Puyallup, Washington, United States
- Sibel Blau, MD · Principal investigator
RecruitingFred Hutch Cancer Center
Seattle, Washington, United States
- Lynn Symonds, MD · Principal investigator
Not yet recruitingMultiCare Cancer Institute
Tacoma, Washington, United States
- Beth Parker · Contact509-746-3222Beth.Parker@multicare.org
- Blair Irwin, MD · Principal investigator
RecruitingWest Virginia University
Morgantown, West Virginia, United States
- Kaitlyn Hager · Contact304-293-0609kaitlyn.hager@hsc.wvu.edu
- Bei Jiang, MD · Principal investigator
RecruitingUniversity of Wisconsin
Madison, Wisconsin, United States
- Briana Barrow · Contact318-212-8671bbarrow@wkhs.com
- Kari Wisinski · Principal investigator
Not yet recruiting
Study team
Sponsor
Natera, Inc.
Study ID 25-085-NCP
Study director
Angel Rodriguez, MD
Natera, Inc.
Frequently asked questions
The sponsor hasn't published answers to common questions for this trial.