Preoperative Testing of the Anti-Progesterone Mifepristone in Early Stage Breast Cancer

July 3, 2019 updated by: Richard Schwab, University of California, San Diego

A Biomarker Study of Mifepristone in Early Stage Breast Cancer

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Moores UCSD Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female identified as a candidate for primary resection of breast cancer (invasive or ductal carcinoma in situ) by a UCSD Breast Care Unit surgical oncologist
  • Subjects must agree to contact the study coordinator prior to starting any new medications, vitamins or herbals during, or for 2 weeks following, mifepristone use
  • Subjects must agree to abstain from alcohol use while on mifepristone
  • Age ≥18
  • ECOG performance status 0-1
  • Prior to starting mifepristone subjects must have a negative urine (βHCG combo with on-board control) or blood pregnancy test and must be using one of the following acceptable means of birth control prior to starting study drug; Barrier methods or surgically sterile (tubal ligation, hysterectomy or partner with confirmed vasectomy). Alternatively the subject must be one year post-menopausal defined as greater than 12 months without a menstrual cycle
  • Prior to starting mifepristone subjects must meet the following laboratory criteria; Granulocytes > 1.5E9/l (grade ≤ 1); Platelets ≥ 100E9/l; Hemoglobin > 10 g/dl (grade ≤ 1); Creatinine < 1.5x normal reference range (grade ≤ 1); SGOT, SGPT, alk phos ≤ 1x normal reference range; Total bilirubin < 1x normal reference range; Calcium < 11.5 mg/dl (grade ≤ 1); HBsAg = Negative; HCV Ab = Negative; INR < 1.5;
  • Subjects must provide written informed consent

Exclusion Criteria:

  • Not scheduled for surgery within 5 days of enrollment
  • Subjects must not be on any therapy to treat breast cancer prior to surgical resection, specifically medications or recent (within 1 month of diagnostic biopsy) withdrawal of estrogen containing medication (eg. hormone replacement therapy)
  • Subjects must not be on any medications, vitamins or herbals that are; potent inhibitors of cytochrome P450 CYP3A4, or sensitive substrates for cytochrome P450 CYP3A4
  • Subjects may not have any history of significant cardiovascular, renal or hepatic disease requiring ongoing medical therapy or clinical intervention
  • Subjects may not have a history of thrombophlebitis, thromboembolic disorder, or cerebral vascular disease.
  • Subjects may not have any known hypersensitivity to mifepristone
  • Subjects may not have a BMI > 39
  • Subjects may not have an IUD (Intrauterine contraceptive device), chronic adrenal failure, concurrent long term steroid therapy, history of allergy to mifepristone, hemorrhagic disorders or concurrent anticoagulant therapy, or inherited porphyrias

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Mifepristone
Drug: Mifepristone
200mg capsules daily for 5-28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in proliferation by Ki-67 immunohistochemistry.
Time Frame: 5-30 days
5-30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor size
Time Frame: 5-30 days
5-30 days
Expression of related targets following mifepristone exposure
Time Frame: 5-28 days
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.
5-28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Investigators

  • Principal Investigator: Richard B Schwab, MD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2010

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

October 1, 2015

Study Registration Dates

First Submitted

June 4, 2010

First Submitted That Met QC Criteria

June 4, 2010

First Posted (Estimate)

June 7, 2010

Study Record Updates

Last Update Posted (Actual)

July 8, 2019

Last Update Submitted That Met QC Criteria

July 3, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UCSD#100231

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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