Abstract OT3-02-08: Open label, phase 2 safety, efficacy, and pharmacokinetic study of pre-surgical intramuscular and intraductal fulvestrant in women with invasive breast cancer or DCIS undergoing mastectomy or lumpectomy
Authors: Feldman S , Gomberawalla A , Alonso A , Rea J , Quay S , Lawrence R 
Published: March 2017

Abstract
BACKGROUND: Breast cancer (BC) is the leading cause of cancer in women in the United States and the second leading cause of cancer-related death. Currently available options for prevention are oophorectomy, bilateral mastectomy, or medical therapy, such as tamoxifen, raloxifene or aromatase inhibitors. None of these options for prevention are without significant side effects with low patient uptake. This study proposes fulvestrant instilled directly into the breast via the nipple orifices as intraductal therapy. Providing a local therapy into the ducts could reduce the morbidity associated with prevention while potentially better targeting the carcinoma cell. Building on prior studies with cytotoxic agents, this study utilizes the pure anti-estrogen fulvestrant to be injected in up to 5 ducts to determine its effect on BC as well as the safety of this method of administration.
TRIAL DESIGN: An open-label, non-randomized PK study of pre-surgical fulvestrant in women scheduled for mastectomy or lumpectomy. Eligible subjects will be undergoing mastectomy or lumpectomy. The first 6 subjects will be treated with the standard dose of 500 mg intramuscular fulvestrant to establish the reference PK curve. The subsequent 24 subjects will receive fulvestrant by intraductal instillation. Subjects where at least 1 suitable duct is identified will undergo nipple aspiration in order to facilitate duct identification and intraductal infusion of a fulvestrant. A maximum of 5 ducts will receive intraductal infusion of fulvestrant. Across all ducts, the total dose will not exceed 500 mg (10 mL). Subsequent to mastectomy or lumpectomy subjects will undergo serial blood draws to determine fulvestrant blood concentration levels and tissue drug levels.
ELIGIBILITY: Female, age &gt; 18, mastectomy/lumpectomy scheduled within 30 days, Stage 1/2, ER+ low grade invasive BC or DCIS, ECOG scale 0-1.
Primary Objective: The safety and tolerability of intraductal administration of fulvestrant in women with Stage 1 or 2 invasive ductal carcinoma or DCIS, prior to mastectomy or lumpectomy.
Secondary Objectives: The pathological effects, specifically changes in Ki67, ER/PgR expression between pre-fulvestrant biopsy and post-fulvestrant surgical specimen.
STATISTICAL METHODS: Aim of this study is to assess safety and tolerability in subjects receiving intraductal fulvestrant. In addition this trial aims to characterize the PK of this alternative route of administration, and compare the intraductal PK profile to that of standard intramuscular administration. Finally, the 6 study subjects who receive intramuscular fulvestrant will be qualitatively compared with the main study cohort of 24 subjects who receive intraductal fulvestrant. Change in Ki67 labeling index will be compared between the two time points (baseline or time of diagnostic biopsy v. time of the surgically excised specimen collection).
CONTACT INFO: Sheldon Marc Feldman MD Columbia University Medical Center sf2388@cumc.columbia.edu 212-305-9676.
Citation Format: Feldman S, Gomberawalla A, Alonso A, Rea J, Quay S, Lawrence R. Open label, phase 2 safety, efficacy, and pharmacokinetic study of pre-surgical intramuscular and intraductal fulvestrant in women with invasive breast cancer or DCIS undergoing mastectomy or lumpectomy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-02-08.