Metastasis is the primary cause of death from breast cancer, invasive carcinoma cells in mouse and rat mammary tumors co-migrate accompanied by macrophages towards intravasation sites . The intravasation occurs at sites where a TIE2-expressing macrophage, a mena-expressing tumor cell, and an endothelial cell are in direct contact, forming a micro-anatomic structure called tumor micro-environment of metastasis (TMEM). Ablation of the presence or activity of the TMEM associated macrophages blocks intravasation at TMEM demonstrating an essential role of perivascular macrophages in TMEM function. Rebastinib, a TIE2 inhibitor , blocks TMEM assembly and function in-vivo and in-vitro assays. We hypothesize that rebastinib combined with antitubulin therapy (eribulin or paclitaxel) could improve clinical outcomes in breast cancer by preventing intravasation at TMEM sites and preventing further metastasis.
The purpose of this study is to determine the safety and tolerability of rebastinib when combined with antitubulin therapy with paclitaxel or eribulin in patients with advanced breast cancer.