Biomarker-guided treatment for breast cancer in postmenopausal women

NeoTAILOR: A Phase II Biomarker-directed Approach to Guide Neoadjuvant Therapy for Patients With Stage II/III ER-positive, HER2-negative Breast Cancer

This study is testing if using specific biomarkers can help doctors choose better treatments for postmenopausal women with certain types of breast cancer, especially to see if some patients can skip chemotherapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 81 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Washington University School of Medicine (other)
• Drugs / interventions: chemotherapy, cyclophosphamide, doxorubicin
• Locations: 1 site (St Louis, Missouri)
• Trial ID: NCT05837455 on ClinicalTrials.gov

What this trial studies

This study aims to improve neoadjuvant treatment selection for postmenopausal women with stage II/III ER-positive, HER2-negative breast cancer by utilizing a biomarker-driven approach. It focuses on identifying patients who may not require chemotherapy based on their Ki67 levels and PAM50 molecular subtypes. The study also emphasizes outcomes in Black patients, addressing disparities in breast cancer treatment. Participants will undergo specific assays and treatments based on their risk category determined by these biomarkers.

Who should consider this trial

Good fit: Ideal candidates include postmenopausal women with newly diagnosed clinical stage II or III ER-positive, HER2-negative breast cancer.

Not a fit: Patients with non-ER-positive or HER2-positive breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more personalized treatment plans and potentially reduce unnecessary chemotherapy for certain patients.

How similar studies have performed: Other studies have shown promise in biomarker-driven approaches for breast cancer treatment, indicating potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

* Histologically or cytologically confirmed newly diagnosed clinical stage II or III (by AJCC 8th edition - at least T2, any N, M0 or if N1+ then any T) ER-positive (ER \> 10%), any PR, and HER2-negative breast cancer with complete surgical excision of the breast cancer after neoadjuvant therapy as the treatment goal.

  * HER2 negative must be assessed by FISH or IHC staining 0 or 1+ according to ASCO/CAP guidelines.
* A palpable mass is not required; however, tumor size must be either:

  * ≥2 cm in one dimension by clinical or radiographic examination (WHO criteria), if clinically axillary lymph node negative OR
  * Measureable (≥10 mm) by modified RECIST v1.1 for breast MRI (see Section 9.0), if histologically confirmed resectable locoregional nodal involvement.
* ECOG performance status 0 or 1.
* Eligible to receive neoadjuvant aromatase inhibitor, as per treating physician.
* Eligible to receive neoadjuvant standard of care anthracycline- and/or taxane-based chemotherapy regimen, as per treating physician.
* Able to tolerate breast MRI with intravenous contrast administration. Must be able to complete the applicable MRI screening evaluation form.
* Adequate bone marrow and organ function, as determined by the treating physician.
* Known history of hepatitis C virus (HCV) infection is permissible provided the patient has been treated and cured.
* At least 18 years of age.
* Postmenopausal status, defined as one of the following:

  * Age ≥ 60 years
  * Age \< 60 with intact uterus and amenorrhea for 12 consecutive months or more
  * Status post bilateral oophorectomy, total hysterectomy
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable), and willing and able to comply with scheduled visits and treatment schedule.

Exclusion Criteria:

* Inflammatory breast cancer (cT4d disease as per AJCC 8th edition).
* Locally recurrent or metastatic disease (cM1 disease as per AJCC 8th edition).
* Bilateral breast cancer.
* Prior systemic therapy for the indexed breast cancer.
* Pre-existing Grade ≥2 neuropathy.
* Uncontrolled intercurrent illness that would limit compliance with study requirements.
* A history of other malignancy ≤5 years prior to the indexed breast cancer diagnosis with the following exceptions:

  * Basal cell or squamous cell carcinoma of the skin which were treated with local resection only
  * Adequately treated carcinoma in situ of the cervix.
  * Prior or concurrent malignancy whose natural history or treatment will not interfere with the safety or efficacy assessments of the indexed breast cancer. In this event, review and approval by the study PI is required.
* Concurrent participation in any investigational therapeutic trial for treatment of breast cancer.
* Known HIV positivity that in the judgement of the treating physician would impact safety of chemotherapy receipt.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to anastrozole, taxanes (paclitaxel or nab-paclitaxel), anthracyclines (doxorubicin or epirubicin) or cyclophosphamide.
* Evidence of uncontrolled ongoing or active infection, requiring parenteral anti-bacterial, anti-viral, or anti-fungal therapy ≤ 7 days prior to administration of study treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
* Any uncontrolled medical condition that in the opinion of the Investigator would pose a risk to participant safety or interfere with study participation or interpretation of individual participant results.

Where this trial is running

St Louis, Missouri

• Washington University School of Medicine — St Louis, Missouri, United States (RECRUITING)

Study contacts

• Principal investigator: Nusayba Bagegni, M.D. — Washington University School of Medicine
• Study coordinator: Nusayba A Bagegni, M.D.

Conditions: Breast Cancer, Cancer of the Breast, breast cancer, postmenopausal women, Ki67, PAM50 subtype, breast cancer disparities