Protocol Number: 00-D-0183

Title:

Effects of the Aromatase Inhibitor Letrozole on Pubertal Progression and Indices of Bone Turnover in Girls with Precocious Puberty and McCune-Albright Syndrome (MAS)

Number:

00-D-0183

Summary:

This study will test the safety and effectiveness of letrozole in treating precocious (early) puberty in girls with McCune-Albright syndrome (MAS). The physical changes of puberty, such as breast enlargement, menstruation and growth spurt, as well as the emotional changes of this developmental stage, usually begin in girls between the ages of 8 and 14. Girls with MAS, however, often begin puberty before age 7. In MAS, large ovarian cysts produce high levels of estrogens (female hormones) that cause the changes of puberty. Children with MAS also have polyostotic fibrous dysplasia (PFD), a disease of bones that, depending on what parts of the skeleton are affected, can lead to broken bones or disfigurement of the head, face, arms and legs, or can cause pressure on nerves and blood vessels. Many children with MAS have cafe-au-lait spots (increased pigmentation) on areas of their skin as well.

Letrozole is an estrogen-lowering drug that has been approved for treating women with breast and other cancers. Although the drug has not been tested or approved for use in children, some pediatric specialists have given it to girls with precocious puberty and MAS and found that it improves their condition without harmful side effects. This study will examine whether letrozole can lower estrogen in girls with MAS and arrest puberty. It will also study the drug's effects on substances involved in bone growth, including calcium, phosphate and amino acids.

Girls 1 to 8 years old with MAS may be eligible for this study. Patients who were enrolled in NIH protocol 98-D-0145 (Screening and Natural History of Patients with Polyostotic Fibrous Dysplasia and the McCune-Albright syndrome) are also eligible. Participants will be admitted to the hospital for 2 to 3 days every 3 months for 15 months, for a total of 6 visits. They will undergo a complete history and physical examination and routine blood and urine tests every visit, as well as evaluations of their general health, growth and bone development, endocrine system (hormone-secreting glands) status and PFD status. A hand X-ray will be taken at the first visit and every 6 months to measure bone age advance. The children will begin taking letrozole at the second visit and continue the drug for 6 months. They will be evaluated after 3 months and 6 months on the drug (visits 3 and 4), and again after 3 months and 6 months after stopping treatment (visits 5 and 6).

Parents of children who weigh more than 18 kilograms (about 40 pounds) may be asked if extra blood may be drawn after 3 months (visit 3) and 6 months (visit 4) of treatment to measure letrozole levels. The blood will be drawn before the morning dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours after the dose through an indwelling needle placed in the vein for 8 to 24 hours.

Parents will keep a record of all episodes of menstrual bleeding and any other symptoms or complaints. Children who respond well to therapy (decreased menses, slowed breast development, slowed growth and bone age advance) will be offered another 12 months of letrozole treatment.

Sponsoring Institute:

National Institute of Dental And Craniofacial Research (NIDCR)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Eligibility Criteria:

INCLUSION CRITERIA

Patients will be girls age 1-8 years with precocious puberty (menses, and/or breast development, and/or BA greater than plus 2SD [for chronologic age] and/or linear growth rate greater than plus 2SD) and polyostotic fibrous dysplasia due to MAS.

All ethnic groups will be included.

EXCLUSION CRITERIA

Boys with MAS will be excluded.

Patients with clinically significant hepatic and/or renal impairment will be excluded.

Special Instructions: Currently Not Provided

Keywords:

Precocious Puberty

Polyostotic

Fibrous Dysplasia

PFD

Recruitment Keywords:

McCune-Albright Syndrome (MAS)

Conditions:

McCune Albright Syndrome

Polyostotic Fibrous Dysplasia

Precocious Puberty

Investigational Drug(s):

Letrozole

Investigational Device(s):

None

Contacts:

Penelope P. Feuillan, M.D.
National Institutes of Health
Building 49
Room 4A28
49 Convent Drive
Bethesda, Maryland 20892
Phone: (301) 594-0309
Fax: (301) 402-0574

Electronic Address: pfeuillan@nhgri.nih.gov

Citations: Not Provided

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Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/16/2004