This phase II trial studies how well two different anti-cancer treatment regimens which both contain trastuzumab and pertuzumab, but with different combinations of chemotherapy work in shrinking cancer before surgery in patients with localized Her2 positive breast cancer. Trastuzumab and pertuzumab are forms of “targeted therapy” because they work by attaching to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab or pertuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body’s immune system. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving trastuzumab with pertuzumab, in addition to combination chemotherapy has been shown to be very effective in shrinking cancer before surgery in patients with Her2 positive locally advanced breast cancer. This trial aims to help determine which regimen may work best with the least toxicity.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03329378.
PRIMARY OBJECTIVE:
I. Determination of pathologic complete response (pCR) rates, defined by the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0 ypN0 in the current American Joint Committee on Cancer [AJCC] system).
SECONDARY OBJECTIVES:
I. Determination of cardiac toxicity as measured by: composite of left ventricular ejection fraction (LVEF), longitudinal strain and troponin.
II. Breast conservation rates.
III. Overall survival.
OUTLINE: Patients are randomized to 1 of 2 regimens.
REGIMEN I: Patients receive doxorubicin intravenously (IV) and cyclophosphamide IV on day 1, and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15, trastuzumab IV on day 1, and pertuzumab IV every 3 weeks. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
REGIMEN II: Patients receive docetaxel IV, carboplatin IV, trastuzumab IV, and pertuzumab IV on day 1, and pegfilgrastim SC on day 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 1 year.
Lead OrganizationIcahn School of Medicine at Mount Sinai
Principal InvestigatorAarti S. Bhardwaj
