Phase II Palbociclib with Fulvestrant in Individuals with Hormone Receptive Positive HER2 Negative Metastatic Breast Cancer who progressed on treatment with Palbociclib + an Aromatase Inhibitor
Objective
Primary To estimate progression-free survival (PFS) of palbociclib and fulvestrant in women and men with ER/PR-positive, HER2-negative MBC who progressed on a palbociclib and an AI To determine the prevalence of ESR1 and PI3K mutations in tissue and in ptDNA in women and men with ER/PR-positive, HER2-negative MBC who progressed on a palbociclib and an AI Secondary To evaluate the PFS in individuals with or without ESR1 mutations when treated with palbociclib and fulvestrant To evaluate the PFS in individuals with or without P13K mutations when treated with palbociclib and fulvestrant To correlate mutation burden, characterized by the number of exome mutations and ptDNA, with PFS and overall survival (OS) To describe measures of disease control, including response rate (RR) and clinical benefit rate (CBR) To assess the safety and tolerability of palbociclib and fulvestrant in individuals who progressed on prior palbociclib and an AI To determine change in CTC enumeration, CTC-ER status, and CTC-Ki67 in individuals when treated with palbociclib and fulvestrant To correlate CTC enumeration, CTC-ER status and CTC-Ki67 with PFS, RR, CBR, and OS To determine if baseline CTC-ESR1 and CTC-other ER-related genes are mutated in individuals progressing on AI and palbociclib therapy To compare CTC-ESR1 and cell free circulating plasma tumor ESR1 mutations Exploratory To describe alterations in genes and gene products relevant to cell cycle, drug targets, tumor sensitivity and resistance To systematically identify novel protein kinases activated in biopsies To conduct additional correlative studies to determine associations between specific kinases identified and response
