Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Carcinoma in Situ

Carcinoma, Ductal

Carcinoma, Intraductal, Noninfiltrating

Breast Diseases

Skin Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Carcinoma In Situ

Reproductive Control Agents

All Drugs and Chemicals

Mifepristone

Progesterone

Contraceptive Agents

Contraceptives, Oral

Contraceptive Agents, Female

Contraceptives, Postcoital

Hormones

Hormone Antagonists

Contraceptive Agents, Hormonal

Richard B Schwab, MD

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.

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.

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

A Biomarker Study of Mifepristone in Early Stage Breast Cancer

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.

University of California, San Diego

Associate Clinical Professor of Medicine

Mifepristone 200 mg will be administered orally

Fa-Chyi Lee, M.D.

The purpose of this study is to see if mifepristone prevents worsening of your cancer. Mifepristone is an antiprogesterone agent, a drug which blocks female hormones, that is commonly used for the termination of pregnancies. It has not been approved by the Food and Drug Administration for use in the treatment of cancer. It is unlicensed in the United States for your condition. However, previous work has indicated that mifepristone may be useful due to how it works. It is being made available for use in the United States for compassionate use through the Feminist Majority Foundation.

This is a compassionate use of mifepristone treatment for patients with conditions that could respond to an antiprogesterone agent, including:

* Meningioma.
* Breast cancer
* Colon Cancer
* Endometrial Stromal Sarcoma
* Bilateral Chronic Central Serous Retinopathy
* Cushing's Syndrome
* Metastatic Adrenocortical Cancer
* Ovarian Cancer
* Other conditions as determined by the attending physicians

Compassionate Use of Mifepristone in Brain/Nervous System and Other Cancers

INST 0817: Compassionate Use of Mifepristone

The time from patient entry into the protocol to death by any cause.

The time from the date of response (not the beginning of treatment unless there is stable disease) to disease progression. Response and progression are evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Frequency and severity of adverse events will be tabulated using counts the following events of interest, which are related to possible adrenal insufficiency: nausea, vomiting, lethargy, dizziness, fatigue, anorexia, and skin rash. Any grade of these events that are self-reported by patients as well as events identified by physician assessment (e.g. physical exam) will be included.

The Feminist Majority Foundation

New Mexico Cancer Care Alliance

200 mg RU-486 (Mifepristone) daily

Mifepristone: Mifepristone 200 mg will be administered orally

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

This is a compassionate use protocol. No statistical analysis was specified in the protocol; it states that only descriptive data will be collected. Data from only 4 patients should not be considered reliable.

Dr. Fa-chyi Lee

Only one patient achieved stable disease. This patient's duration of response could therefore be reported. The other three patients progressed on treatment.

Duration of Response

Nausea

Vomiting

Lethargy

Dizziness

Fatigue

Anorexia

Skin Rash

All patients received at least one dose of study medication and are included in this analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative Testing of the Anti-Progesterone Mifepristone in Early Stage Breast Cancer	NCT01138553	Invasive Breast... Ductal Carcinom...	Mifepristone	18 Years -	University of California, San Diego
Compassionate Use of Mifepristone in Brain/Nervous System and Other Cancers	NCT00832871	Cancer	Mifepristone	18 Years -	New Mexico Cancer Care Alliance
Compassionate Use of Mifepristone in Brain/Nervous System and Other Cancers	NCT00832871	Cancer	Mifepristone	18 Years -	New Mexico Cancer Care Alliance

Spots Global Cancer Trial Database for antiprogesterone