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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.
• Устройство 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.
• Препарат 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.
• Препарат Combination anthracycline and/or taxane based treatment
  Standard of care

Первичные конечные точки

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

Вторичные конечные точки (4)

• Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment [Срок оценки: Through completion of surgery (estimated to be 6 months)]
• Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment [Срок оценки: Through completion of surgery (estimated to be 6 months)]
• Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group [Срок оценки: 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) [Срок оценки: Through completion of treatment (estimated to be 6 months)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Washington University School of Medicine — St Louis

Идентификаторы

NCT: NCT05837455 · 202305007

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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