Oral CDB-4124 vs. Placebo in Stage I-II Primary Breast Cancer

The purpose of this study is to determine whether or not the medication that blocks the effects of the hormone progesterone (CDB-4124 or Proellex) will decrease the growth rate of breast cancer cells as compared to a placebo. CDB-4124 (also called Proellex) is a medication that works against the hormone, progesterone. The researchers in this study would like to compare changes in breast cancer cells of women who have taken CDB-4124 prior to surgery to those from women who have taken a placebo pill prior to surgery.

PRIMARY OBJECTIVES: I. To test the hypothesis that treatment with the selective progesterone receptor modulator (SPRM) CDB-4124 (telapristone acetate) will have an anti-tumor effect in women with early-stage breast cancer, defined as a significant decrease in tumor proliferation (Ki67 labeling index). SECONDARY OBJECTIVES: I. Measure changes in apoptosis using IHC (cleaved caspase 3 or TUNEL). II. Measure changes in blood estradiol and progesterone levels. III. Compare the breast tissue concentrations of CDB-4124 and its metabolite (CDB4453) to plasma concentrations at the end of therapy. IV. Assess adverse events. TERTIARY OBJECTIVES: I. Measure protein expression of related targets (including estrogen receptor alpha (ERA), estrogen receptor beta (ERB), progesterone receptor isoforms progesterone receptor alpha \[PRA\], progesterone receptor beta \[PRB\], tumor necrosis factor receptor superfamily, member 11a, NFKB activator \[RANK\], tumor necrosis factor (ligand) superfamily, member 11 \[RANKL\], and either cyclin-dependent kinase 2 \[cdk2\] or cyclin-dependent kinase 4 \[cdk4\],) using IHC at baseline and after treatment. II. Perform ribonucleic acid (RNA) microarray analysis comparing tumors and normal tissue from the intervention and control groups. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive telapristone acetate orally (PO) once daily (QD) for 2-10 weeks and then undergo surgical resection. ARM II: Patients receive placebo orally once daily for 2-10 weeks and then undergo surgical resection. After completion of study treatment, patients are followed up for 1 month.