Signatera-Guided CDK4/6 Inhibitor Therapy in Breast Cancer

Recruiting now · Not applicable

Conditions studied: Breast Neoplasms, Carcinoma, Ductal, Breast, Receptors, Estrogen (for ER-positive Requirement)

In brief

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.

Key facts

Study ID

NCT07214532

Run by

Natera, Inc.

People needed

725

Starts

2026-03-24

Expected to finish

2037-12-30

Last updated by the study team

2026-04-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You 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 either:
• N1 or,
• If N0, T2 or T3 with G2-3 and/or Ki67≥20% (testing for Ki67 not mandatory), excluding G1.
• 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 may not qualify 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 signature. 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.

Where it is running

• Stockton Hematology Oncology Medical Group — Stockton, California, United States (enrolling)
• Northwest Cancer Center — Dyer, Indiana, United States (enrolling)
• Honor Health Research Institute — Scottsdale, Arizona, United States
• University of Arizona Cancer Center — Tucson, Arizona, United States
• Adventist Health/AIS Cancer Center — Bakersfield, California, United States
• Marin Cancer Care — Greenbrae, California, United States
• Loma Linda University — Loma Linda, California, United States
• UCLA David Geffen School of Medicine — Santa Monica, California, United States
• Kaiser Permanente NorCal — Vallejo, California, United States
• Hartford Healthcare Institute — Hartford, Connecticut, United States
• Yale Cancer Center — New Haven, Connecticut, United States
• Baptist MD Anderson — Jacksonville, Florida, United States
• Mayo Clinic Florida — Jacksonville, Florida, United States
• Jupiter Medical Cancer — Jupiter, Florida, United States
• Miami Cancer Institute — Miami, Florida, United States
• Ocala Oncology — Ocala, Florida, United States
• Northwestern University — Chicago, Illinois, United States
• New England Cancer Specialists — Westbrook, Maine, United States
• Karmanos Cancer Center - Wayne State University — Detroit, Michigan, United States
• Cancer & Hematology Centers — Grand Rapids, Michigan, United States
• Munson Medical Center Cowell Family Cancer Center — Traverse City, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Mercy Health - Sindelar Cancer Center — St Louis, Missouri, United States
• Mercy Health - Pratt Cancer Center — St Louis, Missouri, United States
• Cooper Health — Camden, New Jersey, United States

Full record on ClinicalTrials.gov

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