This phase 1b trial studies the biologic effect of 9cUAB30 on early stage breast cancer. 9cUAB30 is a retinoid X receptor (RXR)-selective retinoid that acts in a tissue selective manner with the goal of minimizing side effects, a necessary feature of agents under development for cancer prevention.
PRIMARY OBJECTIVE: I. Compare molecular analysis of pre- and post-treatment tissue samples of breast cancers of patients treated with 14-28 days of oral retinoid X receptor (RXR)-selective retinoid 9cUAB30 (9 cUAB30) will demonstrate significantly reduced proliferation. SECONDARY OBJECTIVES: I. Determine if 14-28 days of oral RXR-selective 9c-UAB30 treatment increases apoptotic index, as measured by cleaved caspase 3 assay. II. Examine the differences in gene expression from baseline to post-exposure breast cancer samples using a custom gene panel from Nanostring Technologies. III. To examine if the maximum concentration (Cmax) and safety of 9cUAB30 in the first 5 participants is affected by reducing the number of capsules at the 240 mg dose level. IV. To examine the Cmax of all participants at baseline and on the day of surgery. V. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase gene expression of type I immune cells in the tumor immune environment of all participants except the first 5. VI. Assess the overall safety of 9cUAB30 in comparison with known retinoid toxicity. EXPLORATORY OBJECTIVE: I. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase activated type I dendritic cells in peripheral blood. OUTLINE: Patients receive retinoid 9cUAB30 orally (PO) once daily (QD) for 14 to 28 days. Patients then undergo tumor resection surgery. Patients undergo blood and urine sample collection throughout the study. After completion of study treatment, patients are followed up at 7 days and 4-5 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
27
Undergo blood and urine sample collection
Given PO
Undergo tumor resection surgery
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Northwestern University
Chicago, Illinois, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Absolute Change in Ki-67 Expression in Breast Epithelial Cells of Patients Treated With 9cUAB30
Ki-67 was analyzed using immunohistochemistry. Absolute change was measured in looking at the baseline in comparison to that at the end of treatment.
Time frame: Baseline up to 28 days (post-exposure)
Change in Apoptosis in Breast Epithelial Cells of Patients Treated With 9cUAB30
Will be assessed by caspase 3 assays and immunohistochemistry. Change between the treated and matched controls will be summarized with descriptive statistics. Difference in apoptosis will be compared between treatment and matched "control" group using a one-tailed paired t-test or Wilcoxon signed-rank test, as appropriate, at a significance level of 0.05.
Time frame: Baseline up to 28 days (post-exposure)
Change in Gene Expression of Breast Cancer Samples Using a Custom Gene Panel From Nanostring Technologies
Change in gene expression will be summarized with descriptive statistics.
Time frame: Baseline up to 28 days (post-exposure)
Change in Maximum Concentration (Cmax)
Will be tested by a one-sided one-sample student t-test.
Time frame: Pre-dose, 5 minutes, and 2 hours post-dose
Incidence of Observed Adverse Events
Will be graded according to Common Terminology Criteria for Adverse Events version 4.0. Will be compared to know retinoid toxicity. These will be described in descriptive statistics and analyzed.
Time frame: Up to 28 days
Change in Activated Type I Dendritic Cells in Peripheral Blood
Time frame: Baseline up to 28 days (post-exposure)
Determine if Treatment With 2-4 Weeks of 9cUAB30 Prior to Surgery Will Increase Gene Expression of Type I Immune Cells in the Tumor Immune Environment of All Participants
Time frame: Baseline up to 28 days (post-exposure)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.