NeoTAILOR: A Phase II Biomarker-directed Approach to Guide Neoadjuvant Therapy for Patients With Stage II/III ER-positive, HER2-negative Breast Cancer
概览
- 阶段
- 2 期
- 干预措施
- Anastrozole
- 疾病 / 适应症
- Breast Cancer
- 发起方
- Washington University School of Medicine
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)
- 状态
- 招募中
- 最后更新
- 19天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
High-risk endocrine-sensitive group
* 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.
干预措施: Anastrozole
Low-risk group
* 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.
干预措施: VENTANA MIB-1 Ki67 assay
Low-risk group
* 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.
干预措施: Oncotype DX® Recurrence Score
Low-risk group
* 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.
干预措施: PAM50-based Prosigna breast cancer gene signature assay
High-risk endocrine-sensitive group
* 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.
干预措施: VENTANA MIB-1 Ki67 assay
High-risk endocrine-sensitive group
* 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.
干预措施: Oncotype DX® Recurrence Score
High-risk endocrine-sensitive group
* 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.
干预措施: PAM50-based Prosigna breast cancer gene signature assay
High-risk endocrine-resistant group
* 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.
干预措施: VENTANA MIB-1 Ki67 assay
High-risk endocrine-resistant group
* 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.
干预措施: Oncotype DX® Recurrence Score
High-risk endocrine-resistant group
* 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.
干预措施: PAM50-based Prosigna breast cancer gene signature assay
High-risk endocrine-resistant group
* 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.
干预措施: Combination anthracycline and/or taxane based treatment
Low-risk group
* 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.
干预措施: Anastrozole
结局指标
主要结局
Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)
时间窗: Through completion of treatment (estimated to be 6 months)
* 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.
次要结局
- Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment(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))
- 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-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole)(Through completion of treatment (estimated to be 6 months))