Clinical trial NCT05837455: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Cancer of the Breast
Keywords: breast cancer
postmenopausal women
Ki67
PAM50 subtype
breast cancer disparities
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Swim Across America
name: The Foundation for Barnes-Jewish Hospital
First posted: 2023-05-01
Enrollment: 81
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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.
* Tumor size ≥2 cm in one dimension by clinical or radiographic examination (WHO criteria), if clinically axillary lymph node negative. Patients with histologically confirmed resectable locoregional nodal involvement may enroll regardless of tumor size. A palpable mass is not required as long as the mass is at least 2 cm in one dimension by radiographic exam.
* 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 exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or adequately treated carcinoma in situ of the cervix.
* Concurrent participation in any investigational therapeutic trial for treatment of breast cancer.
* Contraindication to breast MRI, such as:

  * Prior allergic reaction to gadolinium-based MR contrast agents.
  * Renal insufficiency (glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2) measured within the past 60 days which precludes safe administration of the contrast agent.
* 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.

Primary outcomes:
measure: Objective response rate (ORR) by breast MRI in the combined low-risk plus high-risk endocrine-sensitive groups (pooled endocrine therapy-responders)
timeFrame: Through completion of treatment (estimated to be 6 months)
Secondary outcomes:
measure: Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment
timeFrame: Through completion of surgery (estimated to be 6 months)
measure: Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment
timeFrame: Through completion of surgery (estimated to be 6 months)
measure: Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group
timeFrame: Through completion of treatment (estimated to be 6 months)
measure: Objective response rate (ORR) by breast MRI in the high-risk endocrine-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole)
timeFrame: Through completion of treatment (estimated to be 6 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Nusayba Bagegni, M.D.
role: PRINCIPAL_INVESTIGATOR
References: