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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05837455
• Other study ID #: 202305007
• Status: Recruiting
• Phase: Phase 2
• Start date: May 30, 2024
• Est. completion date: November 30, 2027

Study information

• Verified date: May 2024
• Source: Washington University School of Medicine
• Contact: Nusayba A Bagegni, M.D.
• Phone: 314-273-3022
• Email: nbagegni[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cancer of the Breast

Intervention

Device:
• 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.
• 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.
• 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.

Drug:
• Anastrozole
Standard of care
• Combination anthracycline and/or taxane based treatment
Standard of care

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	Swim Across America, The Foundation for Barnes-Jewish Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Breast conservation surgery (BCS) conversion rate by cohort and treatment assignment		Through completion of surgery (estimated to be 6 months)
Secondary	Proportion of patients who will require oncoplastic breast reduction surgery before and after neoadjuvant treatment		Through completion of surgery (estimated to be 6 months)
Secondary	Objective response rate (ORR) by breast MRI in the high-risk endocrine-sensitive group	ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to modified 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	Objective response rate (ORR) by breast MRI in the high-risk endocrine-resistant group (high risk patients with week 4 Ki67 > 10% post anastrozole)	ORR is defined as patients achieving clinical complete response (CR) or partial response (PR) according to modified 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)

External Links

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