This phase I trial studies the side effects and best dose of anti-M-CSF monoclonal antibody MCS110 when giving together with dose-dense doxorubicin hydrochloride, cyclophosphamide, and paclitaxel in treating patients with estrogen receptor positive and HER2 negative stage II-III breast cancer. Monoclonal antibodies, such as anti-M-CSF monoclonal antibody MCS110, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, 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 anti-M-CSF monoclonal antibody MCS110, doxorubicin hydrochloride, cyclophosphamide, and paclitaxel may work better in treating patients with breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03285607.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of anti-M-CSF monoclonal antibody MCS110 (MCS110) combined with neoadjuvant dose-dense doxorubicin hydrochloride, cyclophosphamide (ddAC) followed by paclitaxel (T) chemotherapy in patients with estrogen receptor (ER)+ HER2- breast cancer.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of MCS110 treatment in combination with neoadjuvant ddAC followed by T chemotherapy, per Common Terminology Criteria for Adverse Events (CTCAE) criteria.
II. To assess the anti-tumor effects of MCS110 treatment in combination with neoadjuvant ddAC followed by T chemotherapy, as measured by: pathologic complete response-rate (pCR), residual invasive tumor size (RITS), and number of positive axillary lymph nodes.
TERTIARY OBJECTIVES:
I. To assess the effects of MCS110 on the breast tumor immune microenvironment, in combination with neoadjuvant ddAC followed by T chemotherapy.
II. To assess the effects of MCS110 on the bone marrow microenvironment, in combination with neoadjuvant ddAC followed by T chemotherapy.
III. To assess the effects of MCS110 on the peripheral blood cytokine profile, in combination with neoadjuvant ddAC followed by T chemotherapy.
OUTLINE: This is a dose-escalation study of anti-M-CSF monoclonal antibody MCS110.
Patients receive anti-M-CSF monoclonal antibody MCS110 intravenously (IV) over 60-120 minutes every 4 weeks. Courses repeat every 28 days for up to 20 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive doxorubicin hydrochloride IV and cyclophosphamide IV every 2 weeks during weeks 1-8 and paclitaxel IV every week during weeks 9-20 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorLeonel F. Hernandez-Aya
