This phase II trial studies how well palbociclib, letrozole, and trastuzumab work before surgery in treating patients with estrogen receptor (ER) positive and HER2 positive stage II-III breast cancer. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Immunotherapy with monoclonal antibodies, such as trastuzumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving palbociclib, letrozole, and trastuzumab before surgery may work better in treating patients with breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02907918.
PRIMARY OBJECTIVE:
I. To determine the pathologic complete response (pCR) rate in patients with clinical stages II/III ER-positive (+) HER2+ breast cancer treated with neoadjuvant letrozole, trastuzumab, and palbociclib.
SECONDARY OBJECTIVES:
I. To assess safety and tolerability of palbociclib in combination with neoadjuvant letrozole and trastuzumab.
II. To assess the patient reported outcomes associated with palbociclib in combination with neoadjuvant letrozole and trastuzumab.
EXPLORATORY OBJECTIVES:
I. To determine if bone marrow disseminated tumor cells (DTC) status is a good indicator of clinical response and if subpopulations of DTCs emerge with neoadjuvant treatment.
II. To assess intrinsic breast cancer subtype utilizing complementary deoxyribonucleic acid (cDNA) microarray and to correlate with treatment response.
III. To examine the pharmacodynamic effect of the study drug treatment by proteomic and immunohistochemistry analysis of baseline, 2-week and surgical tumor sample, and to correlate with treatment response.
IV. To examine the mutational profiles by whole exome or targeted gene sequencing at baseline and at time of definitive surgery to correlate with treatment response.
V. To assess tumor cell apoptosis index post 2 weeks of palbociclib in combination with letrozole and trastuzumab.
VI. To examine markers of cell proliferation, apoptosis and senescence on 2-week biopsies as predictors of surgical outcome.
VII. To assess serum, plasma, and circulating tumor DNA (ctDNA) sequencing of selected genes, including ESR1, TP53, PIK3CA and retinoblastoma (RB), at baseline, and surgery to correlate with response.
OUTLINE:
Patients receive palbociclib orally (PO) daily on days 1-21, letrozole PO once daily (QD) on days 1-28, and trastuzumab intravenously (IV) over 30-90 minutes (or receive trastuzumab Food and Drug Administration [FDA] approved biosimilar) on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Within 6 weeks after the end of course 4, patients undergo surgery. Courses with letrozole continue until the day of surgery, and courses with trastuzumab continue every 3 weeks until the day of surgery.
After completion of study treatment, patients are followed up for 30-60 days and then yearly for 5 years.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorFoluso Olabisi Ademuyiwa
