Treatment of Uterine Fibroids With the Selective Progesterone Receptor Modulator CDB-2914

Condition(s) targeted: Leiomyomata; Uterine Leiomyomata; Fibroids

Intervention: CDB-2914 (VA2914; ulipristal) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Child Health and Human Development (NICHD)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

This study will evaluate whether the experimental drug CDB-2914 can shrink uterine fibroids in pre-menopausal women. CDB-2914 is chemically similar to Mifeprex (also known as RU486). Mifeprex shrinks fibroid tumors and improves the pain of endometriosis. Because the two drugs are chemically similar and have similar effects on the menstrual cycle, it is thought that CDB-2914 may also be useful in treating fibroids and endometriosis. This study will also see if daily use of CDB-2914 affects the body's adrenal gland function, since it is chemically similar to the stress hormone cortisol, which is produced by the adrenal glands.

Women between 25 and 50 years of age who have regular menstrual cycles and a history of uterine fibroids that cause heavy bleeding, pressure, or pain may be eligible for this study. Candidates are screened with a medical history and physical examination, including breast and pelvic examination, blood and urine tests, a quality-of-life questionnaire, and a home urine test for LH (leuteinizing hormone) surge. They are given a diary to record the LH surge, days of vaginal spotting or bleeding, and symptoms. Participation includes the following:

(Baseline Studies (First Menstrual Cycle)

- Magnetic resonance imaging (MRI): The subject lies in the MRI scanner, a narrow cylinder

with a strong magnetic field, for imaging the uterus.

- Saline hysterosonogram: This is an ultrasound examination of the uterus. A speculum is

placed in the vagina and a small amount of liquid is inserted into the uterus. A probe is then inserted into the vagina. The probe emits and receives sound waves that are used to visualize the fibroids and surrounding structures.

Study Drug Phase (Second through Fourth Menstrual Cycles)

- Subjects are randomly assigned to take CDB-2914 or placebo (inactive compound) once a

day by mouth on an empty stomach for three menstrual cycles or up to 102 days if menstrual cycles are irregular or stop.

- Pregnancy test on first or second day of every menstrual cycle.

- Blood tests every 2 weeks to measure effects of study medication on hormones, blood

count, blood chemistries and liver function.

- 24-hour urine collections three times during the study, about once a month, to measure

cortisol and check adrenal gland function.

- Repeat transvaginal ultrasound after 4-6 weeks of study drug to check fibroid growth.

- Repeat hysterosonogram and MRI within 2 weeks of surgery to count and measure the

fibroids.

Surgery

Women who are candidates for surgical removal of their fibroids and choose to have the surgery are admitted to the Clinical Center for a hysterectomy or myomectomy (removal of fibroids only, leaving uterus intact). Subjects hand in menstrual charts and symptom records and complete a quality-of-life questionnaire. Subjects undergo hysterectomy or myomectomy and remain in the hospital for up to 4 days after surgery. They return to the hospital for a routine checkup 4 to 6 weeks after surgery and are then returned to the care of their physician.

Alternative to Surgery

Women who choose not to have surgery have blood drawn and complete a quality-of-life questionnaire. They may choose to return to the care of their physician or receive CDB-2914 for 3 months, whether or not they received it during the first 3 months of the study. If they choose to take CDB-2914, they have blood tests every 2 weeks and another MRI and ultrasound at the end of the second 3 months.

Official title: Evaluation of Whether the Selective Progesterone Receptor Modulator CDB-2914 Can Shrink Leiomyomata

Study design: Treatment

Detailed description: Uterine leiomyomata (fibroids) are a common benign tumor of the uterine muscle in pre-menopausal women that may cause bleeding, pelvic pain and pressure. Because fibroids grow in the presence of estrogen, medical therapies that decrease estrogen levels (like GnRH analog) cause fibroids to shrink and so may relieve symptoms. However, such medication can only be given short-term and has inconvenient side effects such as hot-flashes. Thus, many women with symptomatic fibroids choose to have them removed surgically, either individually or by removing the uterus via hysterectomy.

This study evaluates whether the progesterone receptor modulator CDB-2914 can shrink fibroids. A similar compound, mifepristone® (Registered Trademark), reduced fibroid size when given for twelve weeks. This study will compare fibroid size, hormone levels and

symptoms before and during daily administration of CDB-2914 (10 or 20 mg) or placebo for 10 -

14 weeks. To do this, women will undergo MRI and a saline hysterosonogram (ultrasound with fluid) of the uterus before and at the end of the study; they will have blood drawn approximately every 14 days, and will fill out a symptom calendar at home. During this initial three month period, women will be randomly assigned to receive CDB-2914 or a placebo and neither the participants nor the investigators will know which a woman receives. At the end of the randomized study period, the research team will offer participants additional options that are not randomized: to receive hysterectomy or myomectomy, or to receive active compound (CDB-2914) for 3 months. Women receiving CDB-2914 during the second three month study phase will be followed with similar blood work and will undergo MRI and a saline hysterosonogram (ultrasound with fluid) of the uterus at the end of the three months. At that time women may choose surgical therapy at the NIH or may elect other treatment options elsewhere.

Minimum age: 25 Years. Maximum age: 50 Years. Gender(s): Female.

Criteria:

- INCLUSION CRITERIA:

Female gender-to evaluate effects in the target population for clinical trials.

History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the ACOG practice bulletin:

Excessive uterine bleeding will be evidenced by either of the following-profuse bleeding with flooding or clots or repetitive periods lasting for more than 8 days; or anemia due to acute or chronic blood loss;

OR

Pelvic discomfort caused by leiomyomata, either acute and severe or chronic lower abdominal or low back pressure or bladder pressure with urinary frequency not due to urinary tract infection.

Uterine leiomyoma(ta) of at least 2 cm size.

In good health. Chronic medication use is acceptable except for glucocorticoid use. Other chronic medication use may be acceptable at the discretion of the research team. Interval use of over-the-counter drugs is acceptable but must be recorded.

Menstrual cycles of 24 - 35 days.

Hemoglobin greater than 10 g/dL (for those wishing surgery); iron may be administered to improve red blood cell counts.

Willing and able to comply with study requirements.

Age 25 to 50.

Using mechanical (condoms, diaphragms) sterilization or abstinence methods of contraception for the duration of the study.

Negative urine pregnancy test.

BMI less than or equal to 33, if a surgical candidate or less than or equal to 35, if not a surgical candidate.

Creatinine less than 1. 3 mg/dL.

Liver function tests within 130% of upper limit.

If interested in hysterectomy, no desire for fertility.

EXCLUSION CRITERIA:

Significant abnormalities in the history, physical or laboratory examination.

Pregnancy.

Lactation.

Use of oral, injectable or inhaled glucocorticoids or megesterol within the last year.

Unexplained vaginal bleeding.

History of malignancy within the past 5 years.

Use of estrogen or progesterone-containing compounds, such as oral contraceptives and hormone replacement therapy, within 8 weeks of study entry, including transdermal, injectable, vaginal and oral preparations.

Use of agents known to induce hepatic P450 enzymes; use of imidazoles.

Current use of GnRH analogs or other compounds that affect menstrual cyclicity.

FSH greater than 20 IU/mL.

Untreated cervical dysplasia.

Need for interval use of narcotics.

Abnormal adnexal/ovarian mass.

Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months.

Contradiction to anesthesia, for women planning surgery.

Genetic causes of leiomyomata.

Previous participation in the study.

Known recent rapid growth of fibroids, defined as a doubling in size in six months.

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129-56. Review.

Starting date: February 2006
Last updated: December 29, 2007