Protocol Number: 06-CH-0090

Title:

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

Number:

06-CH-0090

Summary:

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.

Sponsoring Institute:

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility 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.

Special Instructions:

Currently Not Provided

Keywords:

Endometrium

Progesterone

Estrogen

Fibroid

Hysterectomy

Leiomyoma

Recruitment Keyword(s):

Uterine Fibroids

Fibroids

Condition(s):

Leiomyomata

Uterine Leiomyomata

Fibroids

Investigational Drug(s):

CDB-2914 (VA2914; ulipristal)

Investigational Device(s):

None

Intervention(s):

Drug: CDB-2914 (VA2914; ulipristal)

Supporting Site:

National Institute of Child Health and Human Development

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Batista MC, Cartledge TP, Zellmer AW, Merino MJ, Axiotis C, Loriaux DL, Nieman LK. Delayed endometrial maturation induced by daily administration of the antiprogestin RU 486: a potential new contraceptive strategy. Am J Obstet Gynecol. 1992 Jul;167(1):60-5.

Burroughs KD, Howe SR, Okubo Y, Fuchs-Young R, LeRoith D, Walker CL. Dysregulation of IGF-I signaling in uterine leiomyoma. J Endocrinol. 2002 Jan;172(1):83-93.

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

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