This phase I/II trial studies the side effects and best dose of imipramine before surgery and to see how well it works in treating patients with breast cancer that has spread from where it started in the breast into surrounding, healthy tissue (invasive). Imipramine is a tricyclic antidepressant that may be effective in decreasing the proliferation (multiplying) rate of invasive breast cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03122444.
PRIMARY OBJECTIVE:
I. To determine if imipramine at a dose of 50 mg to 200 mg orally (PO) daily for a period of 21 to 30 days decreases the proliferation rate of triple negative breast cancer, as measured by a change in Ki-67.
SECONDARY OBJECTIVES:
I. To evaluate changes in FoxM1 expression after administration of imipramine for 21 to 30 days in estrogen receptor positive (ER+ ve) and triple negative breast cancer tumors and to assess whether these changes correlate with changes in Ki-67.
II. To assess adverse events and toxicity of imipramine at a dose of 50 to 200 mg orally daily for 21 to 30 days followed by a taper in women with triple negative breast cancer.
III. To evaluate change in gene expression profiles after administration of imipramine for 21 to 30 days in triple negative breast cancer tumors.
EXPLORATORY OBJECTIVE:
I. To determine the effect of imipramine on tumor biology including assessment of breast cancer stem cells and tumor infiltrating lymphocytes.
OUTLINE: This is a dose-escalation study.
Patients receive imipramine PO daily at bedtime (QHS) for 21-30 days in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery or repeat biopsy. Beginning the day after surgery or repeat biopsy, patients receive imipramine PO daily until tapered off.
After completion of study treatment, patients are followed up at 42-51 days.
Lead OrganizationUniversity of Texas Health Science Center at San Antonio
Principal InvestigatorVirginia G. Kaklamani
