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Imipramine before Surgery in Treating Patients with Estrogen Receptor Positive or Triple Negative Breast Cancer

Trial Status: Active

This pilot 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 estrogen receptor positive or triple negative breast cancer. Imipramine is a tricyclic antidepressant that may be effective in decreasing the proliferation (multiplying) rate of estrogen receptor positive or triple negative breast cancer.

Inclusion Criteria

  • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • Previously untreated invasive breast cancer determined by a core needle biopsy
  • A prior, unrelated, breast cancer is allowed
  • All breast cancers with possibility for surgical excision will be included
  • Patient must be able to take oral medications; patients may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the study drug
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (B-hCG) pregnancy test result within 14 days prior to the first dose of imipramine
  • Patients must be eligible for surgical resection of their breast cancer or repeat biopsy after completing treatment
  • Patients must have a complete history and physical examination within 30 days prior to registration
  • Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2
  • Tissue block of initial biopsy specimen is available
  • Patient may not be concurrently enrolled in another investigational drug treatment study

Exclusion Criteria

  • Known diagnosis of bipolar depression or psychosis
  • ECOG 3 or 4
  • Patients planned for pre-operative chemotherapy or those with known metastatic breast cancer
  • Renal impairment defined as estimated glomerular filtration rate (EGFR) < 30
  • Hepatic impairment as judged by clinical investigator or bilirubin > 2
  • As judged by the investigator, severe uncontrolled concurrent medical conditions, psychiatric illness or social condition that would limit compliance with study requirements
  • History of cardiac disease (arrhythmia, conduction abnormality, congenital prolonged QT syndrome, or prolonged corrected QT [QTc] rhythm noted during initial electrocardiogram [EKG] > 480 ms)
  • Current use of selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), monoamine oxidase (MAO) inhibitor, tramadol or trazadone; or use of these agents within 14 days
  • Inflammatory breast cancer
  • Suicidal ideation or history of suicide attempt
  • Myocardial infarction within 3 months of study initiation
  • Patients with angle-closure glaucoma
  • Pregnant or breast-feeding women; as there have been no well-controlled studies conducted with pregnant women to determine the effect of imipramine on the fetus; however, there have been clinical reports of congenital malformations associated with the use of the drug

Texas

San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: ACTIVE
Contact: Virginia G. Kaklamani
Phone: 210-450-3838

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+) 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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

Principal Investigator
Virginia G. Kaklamani

  • Primary ID CTMS 17-0037
  • Secondary IDs NCI-2017-01937
  • Clinicaltrials.gov ID NCT03122444