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

NCT05837455 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 202305007
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer; Cancer of the Breast

Keywords

breast cancer; postmenopausal women; Ki67; PAM50 subtype; breast cancer disparities

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)

  * ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to RECIST v1.1. * Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions thought to be non-malignant should be further investigated before CR can be accepted. * Partial Response (PR): ≥30% decrease in the sum of measures of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD.

  Through completion of treatment (estimated to be 6 months)

Secondary Outcomes (4)

• Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment

  Through completion of surgery (estimated to be 6 months)

• Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment

  Through completion of surgery (estimated to be 6 months)

• Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group

  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)

  Through completion of treatment (estimated to be 6 months)

Study Arms (3)

Low-risk group

EXPERIMENTAL

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw for research purposes at Week 4 (no breast tumor biopsy at this time point) and continue to receive 5 additional 28-day cycles of anastrozole. * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Device: VENTANA MIB-1 Ki67 assay; Device: Oncotype DX® Recurrence Score; Device: PAM50-based Prosigna breast cancer gene signature assay; Drug: Anastrozole

High-risk endocrine-sensitive group

EXPERIMENTAL

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 ≤10% (the high-risk endocrine-sensitive group) will continue to receive 5 additional 28-day cycles of anastrozole. * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Device: VENTANA MIB-1 Ki67 assay; Device: Oncotype DX® Recurrence Score; Device: PAM50-based Prosigna breast cancer gene signature assay; Drug: Anastrozole

High-risk endocrine-resistant group

EXPERIMENTAL

* Baseline breast MRI and research specimen collection prior to the start of treatment with standard of care anastrozole. All patients will have one 28-day cycle of anastrozole, followed by determination of breast cancer risk category by incorporating results from baseline Ki67, Oncotype DX RS, and molecular intrinsic subtype by PAM50. * An additional blood draw and breast tumor tissue collection at Week 4 to assess Ki67. Patients with Week 4 Ki67 \>10% (the high-risk endocrine-resistant group) will receive escalated therapy with \~5-6 additional months of standard of care chemotherapy (combination anthracycline- and/or taxane-based at the discretion of their physician). * After completion of \~6 months of neoadjuvant treatment, will undergo post-treatment breast MRI followed by standard of care surgery.

Device: VENTANA MIB-1 Ki67 assay; Device: Oncotype DX® Recurrence Score; Device: PAM50-based Prosigna breast cancer gene signature assay; Drug: Combination anthracycline and/or taxane based treatment

Interventions

Combination anthracycline and/or taxane based treatment DRUG

Standard of care

High-risk endocrine-resistant group

PAM50-based Prosigna breast cancer gene signature assay DEVICE

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.

High-risk endocrine-resistant group; High-risk endocrine-sensitive group; Low-risk group

Anastrozole DRUG

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.

High-risk endocrine-sensitive group; Low-risk group

VENTANA MIB-1 Ki67 assay DEVICE

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.

High-risk endocrine-resistant group; High-risk endocrine-sensitive group; Low-risk group

Oncotype DX® Recurrence Score DEVICE

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.

High-risk endocrine-resistant group; High-risk endocrine-sensitive group; Low-risk group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Swim Across America: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nusayba Bagegni, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nusayba A Bagegni, M.D.

CONTACT

314-273-3022; nbagegni@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: May 1, 2023
• Study Start: May 30, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)