Know Cancer

or
forgot password

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


Phase 1
1 Year
8 Years
Not Enrolling
Female
McCune Albright Syndrome, Polyostotic Fibrous Dysplasia, Precocious Puberty

Thank you

Trial Information

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


Girls ages 1 - 8 years with the McCune-Albright syndrome (MAS) and girls with other
conditions characterized by precocious puberty due to estrogen hypersecretion from ovarian
cysts will be eligible for this pilot study. Patients who have previously enrolled in
Protocol 98-D-0145 (Screening and natural history of patients with polyostotic fibrous
dysplasia and the McCune-Albright Syndrome) will also be eligible. Patients will be treated
with letrozole, a potent, nonsteroidal aromatase inhibitor, to suppress their elevated serum
estrogen levels. We will confirm the safety and efficacy of letrozole, and study its
effectiveness in controlling the elevated sex steroid levels, and the advanced rates of
linear growth, bone maturation, and pubertal progression in these patients. We will also
study the effect of decreased estrogen levels on the status of their polyostotic fibrous
dysplasia by measuring serum and urine values for bone biomarkers, including calcium,
phosphate, organic amino acids, and vitamin D metabolites, which are known to be abnormal in
many patients with MAS. Patients will act as their own controls. We will compare serum and
urine parameters of pubertal progression and bone biomarkers before, during, and after
discontinuation of letrozole. This trial will be carried out in parallel with in-vitro and
in-vivo laboratory studies using an animal model of fibrous dysplasia. In this model,
osteogenic precursor cells from patient bone biopsies will be cultured in a
hydroxyapatite/tricalcium phosphate matrix and transplanted into immunocompromised mice. We
anticipate that our laboratory findings will complement the care of our patients, resulting
in more effective treatment for the precocious puberty and the bone disease in children with
MAS. Because our initial studies have indicated that letrozole is effective in treating
precocious puberty in MAS patients, this protocol also enrolls girls who have a related
condition, gonadotropin-independent precocious puberty without the bone disease polyostotic
fibrous dysplasia. We also believe that this study complements the recent FDA and NIH
mandates that children be included in the evaluation of pharmaceutical products and in
federally funded clinical research studies.

Inclusion 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.

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

000183

NCT ID:

NCT00006174

Start Date:

August 2000

Completion Date:

May 2009

Related Keywords:

  • McCune Albright Syndrome
  • Polyostotic Fibrous Dysplasia
  • Precocious Puberty
  • Precocious Puberty
  • Polyostotic
  • Fibrous Dysplasia
  • PFD
  • McCune-Albright Syndrome (MAS)
  • Fibrosis
  • Fibrous Dysplasia, Polyostotic
  • Puberty, Precocious
  • Fibrous Dysplasia of Bone

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892