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

The Washington University

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer; Cancer of the Breast

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05837455

202305007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

81 participants in 3 patient groups

Low-risk group

Experimental group

Description:

* 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.

Treatment:

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 group

Description:

* 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.

Treatment:

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 group

Description:

* 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.

Treatment:

Drug: Combination anthracycline and/or taxane based treatment

Device: VENTANA MIB-1 Ki67 assay

Device: Oncotype DX® Recurrence Score

Device: PAM50-based Prosigna breast cancer gene signature assay