SIgnatera-Guided Initiation of Adjuvant CDK4/6 Inhibitor in Intermediate Risk HR+ HER2- Breast Cancer

Plain English Summary

Signatera-Guided CDK4/6 Inhibitor Therapy in Breast Cancer is a Not Applicable clinical trial sponsored by Natera, Inc. studying Breast Neoplasms, Carcinoma, Ductal, Breast, Receptors, Estrogen (for ER-positive Requirement). This trial tests if a special DNA blood test (Signatera) can help decide when to start a type of targeted therapy (CDK4/6 inhibitor) for early-stage breast cancer. It's for patients with intermediate-risk HR+/HER2- early-stage breast cancer who have had surgery. Participants will have regular blood tests to check for tiny amounts of cancer DNA; treatment decisions will be based on these results. Standard hormone therapy is an alternative for some patients, while others may receive hormone therapy plus targeted therapy based on the DNA test. The trial aims to enroll 725 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have had surgery for early-stage breast cancer (HR+/HER2-), and have no contraindications to hormone therapy or specific targeted therapies. You cannot join if you have previously received CDK4/6 inhibitor therapy, have distant metastatic breast cancer, or have certain other active cancers. Specific health conditions and the use of hormone replacement therapy may also exclude you from participating. This trial is studying Breast Neoplasms, Carcinoma, Ductal, Breast, Receptors, Estrogen (for ER-positive Requirement), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to measure 'invasive disease-free survival,' meaning how long patients live without their cancer returning or spreading, to see if the DNA-guided approach is as effective as historica The specific primary outcome measures are: Invasive Disease-Free Survival (From the date of surgery up to 9 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial aims to reduce unnecessary treatment by using a DNA blood test to precisely time the start of CDK4/6 inhibitor therapy for early-stage breast cancer, potentially improving outcomes and redu This research targets Breast Neoplasms, Carcinoma, Ductal, Breast, Receptors, Estrogen (for ER-positive Requirement), where improved treatment options are needed.

Investor Insight

This trial explores a personalized medicine approach for a significant breast cancer subtype, potentially offering a more efficient treatment strategy and representing a growing market for ctDNA-based The large enrollment target of 725 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is right for you, what the potential benefits and risks of the targeted therapy are, and what the Signatera test involves. Participation involves regular clinic visits for blood draws, hormone therapy, and potentially imaging scans over several years. Your treatment will be adjusted based on the results of the Signatera blood test, which checks for circulating tumor DNA. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 725 participants

Interventions

• DEVICE: ctDNA-Guided Treatment Strategy — 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 f

Primary Outcomes

• Invasive Disease-Free Survival (From the date of surgery up to 9 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Signed and dated Informed Consent Form (ICF) obtained prior to any trial-specific screening procedure.
2. Patient is ≥ 18 years-old at the time of ICF signature.
3. Patient is female with known menopausal status at the time of initiation of adjuvant endocrine therapy (ET), or male.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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:
   1. Patients who received neoadjuvant treatment must meet the criteria for stage, grade, Ki67 in any presurgical staging/sample and/or in the surgical specimen.
   2. Categorization into the AJCC 8th edition Anatomic Stage Groups requires determination of the T, N and M categories. ALND can be omitted.
9. Patient has no contraindication to adjuvant ET and is planned to be treated with ET for 5 years (since enrollment date) or more.
10. Provider and patient must be agreeable to initiate CDK4/6 inhibitors only upon ctDNA detection.
11. Patient may have received up to 6 months of standard adjuvant ET at the time of enrollment and any amount of neoadjuvant endocrine therapy.
12. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
13. Patient must not have a clinical contraindication to ribociclib or abemaciclib.
14. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
15. Women of childbearing potential (CBP) must have a confirmed negative serum pregnancy test within 14 days prior to enrollment.
16. 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.

Exclusion Criteria:

1. Patient has had prior exposure to a CDK4/6 inhibitor.
2. Patient is concurrently using hormone replacement therapy.
3. Patient with a known contraindication or hypersensitivity to ribociclib or abemaciclib as per the FDA indication label.
4. Patients with a multicentric and/or multifocal and synchronous contralateral breast cancer are ineligible.
5. 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.
6. 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.
7. 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.
8. 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.

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• Mayo Clinic Arizona, Phoenix, Arizona, United States
• 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
• Stockton Hematology Oncology Medical Group, Stockton, California, United States
• Kaiser Permanente NorCal, Vallejo, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Early-Stage Breast Cancer
• Adjuvant Therapy
• Metastatic Breast Cancer
• Oncology
• Genomics
• Liquid Biopsy
• Cancer Diagnostics

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