Endocrine Sensitive HER2+/HR+ Breast Cancer
Conditions
Keywords
HER2+/HR+, breast cancer
Brief summary
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
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
Interventions
DRUGPertuzumab
* 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).
Sponsors
Association for Translational Research in Oncology (AS.T.R.O.)
Istituto Oncologico Veneto IRCCS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of pathologic complete response | At time of surgery, within 3 weeks from the last i.v. therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of clinical objective response. | At time of surgery, within 3 weeks from the last i.v. therapy | 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. |
| 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 | — |
Countries
Italy
Outcome results
None listed