Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy

Study Overview
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Brief Summary
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Hormonal therapy administered before surgery in ER-positive and HER2-positive patients with breast cancer.

Detailed Description
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Hormonal therapy with fulvestrant 500 mg to be administered before surgery With docetaxel, Trastuzumab, and pertuzumab to determine pathological complete remission rate at the time of surgery in ER-positive and HER2-positive patients with breast cancer.

Official Title
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Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy (Taxotere, Trastuzumab and Pertuzumab) in Patients With HER2-positive and ER-Positive Breast Cancer (NeoHTTP Study)

Conditions
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HER2-positive Breast Cancer, ER-positive Breast Cancer

Intervention / Treatment
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* Drug: fulvestrant 500 mg
* Drug: Docetaxel
* Drug: Trastuzumab (H, 8mg/kg
* Drug: Pertuzumab (P, 840 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age with histologically, and radiographically confirmed non-metastatic ER-positive (defined as ≥30% of positive cells) and HER2-positive (defined as overexpression by immunohistochemistry (3+) or 2+ and positive by defined by fluorescence or dual in situ hybridization.) breast cancer with minimal tumor size over 2 cm (≥T2 lesion) to receive neoadjuvant chemotherapy recommended by the treating physician Eastern Cooperative Oncology Group (ECOG) performance status score < 1 Absolute neutrophil count > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 1.5 X ULN (≤ 3 mg/dL if clinically diagnosed with Gilbert syndrome) AST/ALT ≤ 2.5 X ULN (AST/ALT ≤ 5X ULN if clinically diagnosed with Gilbert syndrome) Women of child-bearing potential (i.e., women who are pre-menoposaul or not surgically sterile) must have a negative serum pregnancy test within 2 weeks prior to beginning treatment Exclusion Criteria: Uncontrolled cardiac disease, such as angina, hypertension or significant arrhythmias LVEF (left ventricular ejection fraction) < 50% on any prior assessment. Note: Assessment of LVEF is done before and after trastuzumab-based chemotherapy as standard of care Pregnant or lactating females Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Protocol<br>Hormonal therapy with fulvestrant 500 mg will be administered intramuscularly on days 1, 15 of the first cycle, and thereafter on day 1 of every 28-day cycle for up to 5 cycles before surgery. Docetaxel (T) 75 mg/m2 every 3 weeks will be given for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery. | Drug: fulvestrant 500 mg<br>* Hormonal therapy with fulvestrant 500 mg will be administered intramuscularly on days 1, 15 of the first cycle, and thereafter on day 1 of every 28-day cycle for up to 5 cycles before surgery.<br>* Other names: fulvestrant;Drug: Docetaxel<br>* Docetaxel (T) 75 mg/m2 every 3 weeks will be given for four cycles.<br>* Other names: Taxotere;Drug: Trastuzumab (H, 8mg/kg<br>* Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery.<br>* Other names: Trastuzumab;Drug: Pertuzumab (P, 840 mg<br>* Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery.<br>* Other names: Pertuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Remission Rate | To determine pathological complete remission rate at the time of surgery in ER-positive and HER2-positive breast cancer patients undergoing neoadjuvant chemoimmunotherapy (docetaxel, trastuzumab, pertuzumab) concurrently with neoadjuvant hormonal therapy with fulvestrant. Note: pCR, defined as the absence of invasive neoplastic cells of the primary tumor in the breast, remaining in-situ lesions are allowed, ypT0-is; | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Pathological Response Rate | Partial pathological response rate at the time of surgery and biomarker changes in breast cancer (biopsy vs residual tumor) before and after neoadjuvant chemotherapy Note: pPR, defined as residual invasive disease of 1cm, ypT1a-b. | One Year | 
| QTA (Quantitative Texture Analysis) | QTA (Quantitative Texture Analysis): will be obtained from baseline mammogram and the correlation with clinical outcome after neoadjuvant therapy will be performed. | One year |