Compare Daily Ulipristal Acetate and Combined Oral Contraceptive Effects on Breast Epithelial Cell Proliferation

• Status: Completed
• Trial end date: 2019-10-21
• Target enrollment: 0
• Participant gender: Female

Summary

Breast cancer accounts for almost a quarter of all cancers in women. In the United States (U.S.) in 2014, more than 230,000 women were diagnosed and 40,000 died of breast cancer. There is an urgent need to develop acceptable means of preventing breast cancer both for high risk and average risk women.

The proposed study is a clinical trial in premenopausal women aged 18-39 to evaluate the capacity of daily Ulipristal Acetate (UPA) to reduce breast epithelial cell proliferation (increase in number of cells in the breast) and to measure its effect compared to that found with a combined estrogen-progestin oral contraceptive (COC). UPA is an anti-progestin in use as daily medication up to 12 months for the treatment of abnormally heavy bleeding at menstruation due to uterine fibroids, and is currently in trials in the U.S. to evaluate its use as a daily contraceptive.

The investigators will use breast biopsies to compare breast cell proliferation, comparing biopsies at the end of 3 months treatment to biopsies taken at baseline in the 2 groups (UPA and COC). The investigators will also compare the changes in the 2 groups to each other. The comparison of the effect of UPA to that of a conventional COC is because of UPA's potential use as a daily contraceptive.

Cell proliferation in the breast occurs throughout the menstrual cycle. The actions of hormones on the breast are rapid and an anti-progestin such as UPA, which will block the action of progesterone in the breast, would be predicted to quickly lower breast cell proliferation in premenopausal women. Effects of UPA on the uterus continue to be studied and are reassuring. COC use has not been found to lower breast cell proliferation and is not associated with any decrease in risk of breast cancer.

The changes in breast cell proliferation will also be compared to changes seen on breast MRI. If the changes are highly correlated future studies will be able to be done without the need for breast biopsies.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Columbia University
• Collaborators: Memorial Sloan Kettering Cancer Center; Weill Medical College of Cornell University
• Treatments: Contraceptive Agents; Contraceptives, Oral; Contraceptives, Oral, Combined; Ulipristal acetate

Criteria

Inclusion Criteria:

1. Women between 18 and 39 years of age (inclusive).

2. In good health, with regular menstrual cycles between 21 and 35 days and with intra-individual variation of less than or equal to 5 days.

3. Volunteers who are postpartum or who aborted in the first or second trimester must have had two normal menstrual cycles (3 bleeding episodes) prior to screening.

4. No use of any other hormonal contraception within two normal menstrual cycles (3 bleeding episodes) prior to screening.

5. If previous use of injectable Depo Provera, subject must have had two normal menstrual cycles (3 bleeding episodes) prior to screening.

6. Not at risk for pregnancy:

1. Using a copper intra uterine device (IUD), or

2. Willing to protect all further acts of intercourse with condoms, or

3. Not hetero-sexually active, or

4. Having undergone previous tubal ligation, or

5. Partner sterilized or vasectomized.

7. Body Mass Index (BMI) < 30 kg/m2 and not having previously undergone bariatric surgery.

8. Diastolic blood pressure (BP) ≤ 90 mm Hg and systolic BP ≤ 140 mm Hg after at least 5 minutes in a sitting position. Hypertensive subjects who are treatment controlled may obtain a waiver for participation.

9. Willing and able to follow all study requirements, including use of the study medication and willing to give information related to study medication use as required during the study, in the opinion of the investigator.

10. Able to give informed consent to participate in the study.

Exclusion Criteria:

1. Currently pregnant as confirmed by positive high-sensitivity urine pregnancy test.

2. Currently breast-feeding or within 30 days of discontinuing breast feeding at screening.

3. Undiagnosed abnormal genital bleeding.

4. Known hypersensitivity to an active substance or any of the excipients of the study treatments.

5. Abnormal clinical breast examination at screening.

6. Suspected hyperplasia or carcinoma of the endometrium.

7. Ovarian cyst > 25 mm observed on transvaginal or transabdominal ultrasound performed on the first visit of the Baseline cycle.

8. History of any diagnostic or therapeutic breast biopsy

9. Any of the known contraindications to COC use:

1. History of or existing breast cancer, or other hormone sensitive neoplasia, or

2. History of or current ischemic heart disease or stroke, or

3. History of or current deep venous thrombosis or pulmonary embolism, or

4. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies, or

5. History of or current benign or malignant liver tumor, or

6. Severe (decompensated) cirrhosis.

7. Headaches with focal neurological symptoms.

10. Hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

11. Known or suspected alcoholism or drug abuse.

12. Known human immunodeficiency virus (HIV) infection.

13. Smoking 15 cigarettes or more per day, if in the opinion of the investigator or medically qualified designee, this would increase the risk for cardiovascular disease and thromboembolism based on risk factors.