Clinical Trial: Trial of Aromatase Inhibition in Lymphangioleiomyomatosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A TRIAL OF LETROZOLE IN PULMONARY LYMPHANGIOLEIOMYOMATOSIS

Brief Summary: The hypothesis in this study is that estrogen suppression by an aromatase inhibitor in postmenopausal women with Lymphangioleiomyomatosis (LAM) will prevent or delay progression of lung disease and result in a decrease in the rate of decline in FEV1

Detailed Summary:

Lymphangioleiomyomatosis, or LAM, is an uncommon, progressive, cystic lung disease that predominantly affects young women. Pulmonary parenchymal changes consistent with LAM are found in about one third of women with tuberous sclerosis complex (TSC), an autosomal dominant tumor suppressor syndrome. LAM also occurs in a sporadic form that is not associated with germ line mutations in TSC genes. Recent evidence that recurrent LAM after lung transplantation results from seeding of the graft from a remote source and suggests a metastatic mechanism for the disease.

Since LAM occurs almost exclusively in women, and exposure to estrogen either exogenously or during pregnancy can exacerbate LAM, estrogen suppression might be expected to prevent or delay progression of disease. In preclinical studies, estrogen induces the growth of TSC2-deficient cells and tumor cells derived from LAM patients. In a xenograft model of lymphangioleiomyomatosis presented by Dr. Yu at the 2008 LAM Research Meeting, estrogen promoted the pulmonary metastases of tuberin-deficient ELT3 cells (TSC2-deficient rat uterine leiomyoma cells) in female ovariectomized CB-17-scid mice, while the estrogen inhibitor fulvestrant completely blocked estrogen-promoted pulmonary metastases. This work was recently published.

Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis)(14). It is chemically described as 4,4'-(1H-1,2,4-Triazol-1-ylmethylene)diben-zonitrile.

In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically
Sponsor: University of Cincinnati

Current Primary Outcome: The effect on Forced Expiratory Volume in one second [ Time Frame: twelve months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Other measures of pulmonary function [ Time Frame: twelve months ]
    FVC, DLCO, TLC,RV, FRC, 6MWT
  • Quality of life measures [ Time Frame: twelve months ]
    Quality of Life, dyspnea and fatigue, functional performance
  • Serum VEGF-D [ Time Frame: twelve months ]


Original Secondary Outcome: Same as current

Information By: University of Cincinnati

Dates:
Date Received: May 11, 2011
Date Started: May 2011
Date Completion:
Last Updated: August 24, 2015
Last Verified: August 2015