This phase II trial studies the side effects of an alternative dosing schedule of palbociclib and letrozole or fulvestrant with or without goserelin acetate in treating patients with hormone receptor positive breast cancer that has spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone can cause the growth of breast tumor cells. Hormone therapy using letrozole, fulvestrant, and goserelin acetate may fight hormone receptor positive breast cancer by blocking the use of estrogen and progesterone by the tumor cells. Giving an alternative dosing schedule of palbociclib and letrozole or fulvestrant with or without goserelin acetate may work better in treating patients with hormone receptor positive breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03007979.
PRIMARY OBJECTIVES:
I. To determine the rate of grade 3 or higher neutropenia in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule within the first 29 days of treatment.
SECONDARY OBJECTIVES:
I. To determine the rate of grade 3 or higher neutropenia in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule during all cycles.
II. To determine the rate of palbociclib dose reduction, interruption, or discontinuation.
III. To determine the adverse events profile of palbociclib given on a 5 days on/2 days off schedule.
IV. To determine the progression free survival in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.
V. To determine the overall response rate (complete response [CR]+partial response [PR]) in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.
VI. To determine the clinical benefit rate (CR+PR+stable disease [SD] for at least 6 months) in patients with hormone receptor positive breast cancer treated with palbociclib on a 5 days on/2 days off schedule.
EXPLORATORY OBJECTIVES:
I. To assess changes in cell free deoxyribonucleic acid (DNA) mutation profile, including mutations in TP53, PIK3CA, ESR1, and RB1 and their correlation with treatment response.
II. To correlate archival tumor mutation profile and retinoblastoma (RB) protein status with treatment response.
III. To assess intrinsic and acquired resistance mechanisms to palbociclib in tumor samples collected at baseline and at progression.
IV. To assess changes in serum thymidine kinase activity and correlate with treatment response and absolute neutrophil count.
V. To establish patient derived xenograft (PDX) models from tumor biopsies before treatment and at progression for future studies.
VI. To assess baseline and changes in circulating tumor cell (CTC) gene expression profiles and to correlate with treatment response.
OUTLINE:
Patients receive palbociclib orally (PO) on days 1-5, 8-12, 15-19, and 22-26. Patients also receive letrozole PO daily on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and day 1 only of each course thereafter per physician choice. Patients who are pre- and peri-menopausal also receive goserelin acetate subcutaneously (SC) on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorCynthia Xiuguang Ma
