NEOADjuvant Aromatase Inhibitor and Pertuzumab/Trastuzumab for Women With Breast Cancer

Study Overview
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Brief Summary
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This is a prospective, single-arm, phase II study of 32 evaluable patients treated with NEOADjuvant Aromatase inhibitor and Pertuzumab/Trastuzumab (NEOADAPT) without chemotherapy for hormone receptor positive (HR+), [i.e. Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+)] HER2+ localized, non-metastatic stage I - IIb breast cancer.

Official Title
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A Phase II Study of NEOADjuvant Aromatase Inhibitor and Pertuzumab/Trastuzumab (NEOADAPT)

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Exemestane
* Drug: Letrozole
* Drug: Anastrozole
* Drug: Leuprolide Acetate
* Drug: Pertuzumab
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide signed, written informed consent Histologically or cytologically confirmed non-metastatic adenocarcinoma of the breast (stage I-II) Candidate for curative-intent treatment ER+ and/or PR+ and HER2-positive (Fluorescence In Situ Hybridization-positive or 3+ by Immunohistochemistry staining) Life expectancy greater than 5 years Left Ventricular Ejection Fraction > 50% at baseline (within 30 days of day 0) Eastern Cooperative Oncology Group performance status ≤2 Absolute Neutrophil Count >1000/µL Platelets ≥50,000/µL Hemoglobin >8.0 g/dL, Creatinine ≤3.0 x upper limit of normal (ULN) Bilirubin ≤3.0 x ULN Aspartate aminotransferase or Alanine aminotransferase <5.0 x ULN Negative serum pregnancy test for women <12 months after the onset of menopause unless surgically sterilized Agreement by women of childbearing potential and male participants with partners of childbearing potential to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Exclusion Criteria: Active infection Presence of known metastases (stage IV disease) Pregnant or lactating women Prior chemotherapy or radiation therapy for the primary breast cancer Concomitant malignancies or previous malignancies within the last 5 years except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary or metabolic disease including diabetes, wound healing disorders, ulcers or bone fractures) Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipated need for major surgery during the course of study treatment Current known infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) or Hepatitis C Virus (HCV) Receipt of intravenous antibiotics for infection within 14 days prior to receiving study treatment Current chronic daily treatment with corticosteroids (dose >10 mg/day methylprednisolone equivalent) except inhaled steroids Known hypersensitivity to any of the study drugs Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol

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: Neoadjuvant Biological Therapy<br>Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals). Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes). Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes) | Drug: Exemestane<br>* Aromatase inhibitor<br>* Other names: Aromasin;Drug: Letrozole<br>* Aromatase inhibitor<br>* Other names: Femara;Drug: Anastrozole<br>* Aromatase inhibitor<br>* Other names: Arimidex;Drug: Leuprolide Acetate<br>* Luteinizing Hormone-Releasing Hormone agonist<br>* Other names: Lupron Depot;Drug: Pertuzumab<br>* Monoclonal antibody (HER2/neu receptor antagonist)<br>* Other names: Perjeta;Drug: Trastuzumab<br>* Monoclonal antibody (HER2/neu receptor antagonist)<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of Pathological Response | The presence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Pathological complete response (pCR) is defined as the absence of residual invasive cancer. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Treatment | Median number of days between Day 0 (first treatment of trastuzumab and pertuzumab) and three weeks after the last dose of neoadjuvant trastuzumab and pertuzumab on treatment protocol. | One year | 
| Evidence of Radiographic Response | Change in dimensions (millimeters) of target lesions (along long axis) and non-target lesions (along long axis for non-lymphatic lesions and short axis for lymph nodes) as observed by Magnetic Resonance Imaging and quantified by modified RECIST 1.1 criteria. | Assessed every 12 weeks up to one year | 
| Measurement of Left Ventricular Ejection Fraction (LVEF) | Determination of cardiac function as measured by echocardiogram or multi-gated acquisition scan (MUGA). | Assessed every 12 weeks up to one year | 
| Mammaprint Genomic Analysis | Mammaprint will estimate the risk level of the subject's tumor. | One year or up to 3 months after definitive surgery |