Presurgical Phase IIB Trial of Oral CDB-4124 vs. Placebo in Women With Stage I-II Primary Breast Cancer
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
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.
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
After completion of study treatment, patients are followed up for 1 month.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Measurable decrease in tumor growth from baseline to time of surgery
Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery to measure if there is a decrease in tumor growth.
Baseline to time of surgery (between 2-10 weeks, up to 10 weeks)
Seema Khan, MD
United States: Institutional Review Board
|Northwestern University||Chicago, Illinois 60611|