Preoperative Testing of the Anti-Progesterone Mifepristone in Early Stage Breast Cancer
This study is currently recruiting participants.
Verified May 2013
by University of California, San Diego
University of California, San Diego
Information provided by (Responsible Party):
Richard Schwab, University of California, San Diego
First received: June 4, 2010
Last updated: May 24, 2013
Last verified: May 2013
History of Changes
Purpose The primary objective of this study is to identify the group of women with early stage breast cancer most likely to benefit from treatment with the selective progesterone receptor modulator (SPRM) mifepristone. This will be done by treating women briefly prior to planned surgery and examining the decrease in growth rate (measured by Ki-67 immunohistochemistry) in tumor samples taken before and after exposure to mifepristone.
Study Type: Interventional Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment Official Title: A Biomarker Study of Mifepristone in Early Stage Breast Cancer
Resource links provided by NLM:
Genetics Home Reference
related topics: breast cancer
related topics: Breast Cancer Cancer
available for: Mifepristone
U.S. FDA Resources
Further study details as provided by University of California, San Diego:
Primary Outcome Measures:
- Change in proliferation by Ki-67 immunohistochemistry. [ Time Frame: 5-30 days ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Tumor size [ Time Frame: 5-30 days ] [ Designated as safety issue: No ]
- Expression of related targets following mifepristone exposure [ Time Frame: 5-28 days ] [ Designated as safety issue: No ]RNA-seq will be used to evaluate expression of steroid receptor isoform expression following drug exposure. These data will be compared with response as measured by proliferation change and tumor size.
Estimated Enrollment: 66 Study Start Date: June 2010 Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Detailed Description: Secondary objectives of this study include; (1) Measuring objective response in tumor size with treatment, (2) Establishing the safety and tolerability of short term mifepristone exposure in early stage breast cancer patients, and (3) Performing exploratory studies of expression of related targets following drug exposure.
Anti-estrogen therapy has been a mainstay of breast cancer treatment for over three decades. It is highly effective and has modest toxicity, certainly in comparison to chemotherapy. The selective estrogen receptor modulator tamoxifen has the longest history but a number of aromatase inhibitors and the anti-estrogen fulvestrant are also in widespread use along with ovarian ablation for pre-menopausal women. Given the success of this approach, and the highly analogous parallel progesterone signal, it is unfortunate that anti-progesterone therapy has not been similarly pursued. Additionally, data from the Woman's Health Initiative trial reveal a potentially significant role for progesterone in breast cancer development and growth. Healthy postmenopausal women treated with the combination of estrogen and progesterone over a 5 year period were 24% more likely to develop invasive breast cancer and had larger tumors at diagnosis. Notably this effect was not seen in post-hysterectomy women treated with estrogen alone over nearly 7 years. In fact a non-statistically significant reduction in breast cancer incidence was observed with estrogen alone.
The anti-progesterone mifepristone has been found to reduce proliferation in normal breast tissue. Even a low dose of mifepristone (50mg every other day for 3 months) demonstrated a statistically significant reduction in breast cell proliferation (measured by Ki-67 immunohistochemistry).
Higher doses of mifepristone, 200mg daily, have been used in patients with metastatic breast cancer for durations of almost 2 years without serious toxicity. Response rates were only 11% but no grade 4 or 5 toxicities occurred. Some grade 3 toxicities occurred, including lethargy, nausea, vomiting, and skin rash. These rashes resolved with temporary discontinuation of drug and did not recur when drug was resumed.
As a whole these data strongly support research into anti-progesterone therapy for early stage breast cancer. To our knowledge this is the first such study.