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

Official title

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

Overview

This study aims to utilize a novel biomarker-driven approach to guide neoadjuvant treatment selection. It is the hypothesis that this will improve clinical response for postmenopausal women with clinical stage II/III ER-positive, HER2-negative breast cancer and identify those who may not require neoadjuvant chemotherapy, with a primary focus on outcomes in Black patients.

Detailed description

Risk category is defined as follows:

* Low risk:

* Baseline Ki67 ≤ 10% (OR) * Luminal A molecular intrinsic subtype by PAM50 * High risk:

* Non-Luminal A molecular intrinsic subtype by PAM50 (OR) * In cases of non-diagnostic PAM50 molecular intrinsic subtype, patients will enroll in the high-risk group and undergo Week 4 tumor biopsy.

Interventions

• Device VENTANA MIB-1 Ki67 assay
  Ki67 scoring determination (standard of care) utilizing the Ki67 MIB-1 assay (clone 30-9) (VENTANA) will be performed at baseline, Week 4 (+/- 14 days - high-risk group only), and at time of surgery in accordance with the International Ki67 in Breast Cancer Working Group guidelines.
• Device Oncotype DX® Recurrence Score
  Oncotype DX® Recurrence Score (RS) testing - assessing expression of 21 genes including 16 cancer-related genes and 5 reference genes - will be performed as standard of care in a central laboratory (Exact Sciences) on RNA extracted from formalin-fixed paraffin-embedded core-biopsy samples.
• Device PAM50-based Prosigna breast cancer gene signature assay
  This PAM50-based Prosigna breast cancer gene signature assay for intrinsic molecular subtype determination will be performed on formalin-fixed, paraffin-embedded (FFPE) core-biopsy samples.
• Drug Anastrozole
  Standard of care. All patients must start on anastrozole at time of enrollment but may switch to another aromatase inhibitor (letrozole or exemestane) due to toxicity or financial/other concerns at discretion of investigator after a discussion with the PI. Every effort to minimize interruption of aromatase inhibitor (AI) therapy is recommended.
• Drug Combination anthracycline and/or taxane based treatment
  Standard of care

Primary outcome measures

• Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders) [Time frame: Through completion of treatment (estimated to be 6 months)]

Secondary outcome measures (4)

• Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment [Time frame: Through completion of surgery (estimated to be 6 months)]
• Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment [Time frame: Through completion of surgery (estimated to be 6 months)]
• Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group [Time frame: Through completion of treatment (estimated to be 6 months)]
• Objective response rate (ORR) by breast MRI in the high-risk endocrine-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole) [Time frame: Through completion of treatment (estimated to be 6 months)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Identifiers

NCT: NCT05837455 · 202305007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗