Preoperative Study With Trastuzumab, Pertuzumab and Letrozole in Breast Cancer Patients Sensitive to Hormonal Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the activity of molecular response in endocrine sensitive breast cancer HER2+/HR+ patients treated with Pertuzumab-trastuzumab plus Ietrozole.

Detailed Description
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The purpose of this study is: to evaluate the rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes. to estimate the percentage of clinical objective responses (cOR) (complete plus partial) in the breast, as assessed by ultrasonography (US) to estimate the percentage of breast conservative surgery to evaluate the safety profile To perform correlative biomarker analyses

Official Title
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PERtuzumab-trastuzumab Plus lEetrozoLe In Endocrine Sensitive Breast Cancer: a Phase II neoAdjuvant Study

Conditions
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Endocrine Sensitive HER2+/HR+ Breast Cancer

Intervention / Treatment
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* Drug: Pertuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: primary diagnosis of infiltrating breast cancer HR positivity (ER ≥ 10% and/or PgR ≥10%) and HER2 positivity (IHC 3+ or FISH/CISH amplification), as assessed by local laboratory. Stage II-IIIA age >18 yrs ECOG Performance Status 0-1 Postmenopausal status, defined by at least one of the following: 60 years of age; < 60 years of age and amenorrheic for >/=12 months prior to day 1 < 60 years of age, without a uterus, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) values within postmenopausal range Prior bilateral oophorectomy Prior radiation castration with amenorrhea for at least 6 months Cardiac ejection fraction within the institutional range of normal (as measured by echocardiogram or MUGA scan). Normal organ and marrow function as defined below: (leukocytes >=3000/mcL; absolute neutrophil count >=1,500/mcL; platelets >=100,000/mcL; total bilirubin within 1.25 x normal institutional limits (with the exception of Gilbert's syndrome); AST (SGOT)/ALT(SGPT) within 1.25 x institutional upper limit of normal creatinine within normal institutional limits Availability of tumor tissue suitable for biological and molecular examination before starting primary treatment Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Stage IIIB, IIIC, and inflammatory breast cancer Stage IV breast cancer Prior treatment with chemotherapy, endocrine therapy or radiotherapy. Prior treatment with HER2 targeting therapies LVEF below the ULN Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) grade II or higher, or serious cardiac arrhythmia requiring medication. Received any investigational treatment within 4 weeks of study start. Subjects with known infection with HIV, HBV, HCV Known hypersensitivity to any of the study drugs or excipients. Dyspnoea at rest or other disease requiring continuous oxygen therapy. Psychiatric illness/social situations that would limit compliance with study requirements Subjects assessed 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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Female

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: Pertuzumab, Trastuzumab, Letrozole<br> | Drug: Pertuzumab<br>* Pertuzumab 840 mg loading dose iv on day one, followed by 420 mg iv every 3 weeks for 5 cycles Trastuzumab 8 mg/kg loading dose iv on day 2, followed by 6 mg/kg iv on day 2 of each subsequent 3 weekly cycle Letrozole 2.5 mg daily p.o. for five 21-day cycles (to be continued until surgery).<br>* Other names: Perjeta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of pathologic complete response | A pathologic complete response (pCR) is defined the complete absence of infiltrating tumor cells in the breast and in lymph nodes. Residual in situ disease (DCIS) will be included in the pCR category. | At time of surgery, within 3 weeks from the last i.v. therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of clinical objective response. | The Clinical Response will be defined according to RECIST criteria comparing the tumor size (largest tumor diameter) before and after treatment, as assessed by ultrasound examination. | At time of surgery, within 3 weeks from the last i.v. therapy | 
| Rate of Conservative Surgery |  | At time of surgery, within 3 weeks from the last i.v. therapy | 
| Safety profile assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) To version 4.0 will be used |  | Every 21-day cycles | 
| Occurrence of mutations in the PIK3CA gene |  | Within 4 weeks prior to first dose treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2+/HR+, breast cancer