Letrozole for Lymphangioleiomyomatosis

Lymphangioleiomyomatosis Clinical Trial

— TRAIL  

Official title:

Trial of Letrozole in Lymphangioleiomyomatosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01353209
• Other study ID #: 5708
• Status: Completed
• Phase: Phase 2
• Start date: May 2011
• Est. completion date: September 2014

Study information

• Verified date: April 2024
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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 germline 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 is exacerbated by pregnancy, menses and hormonal therapies suggest that estrogen suppression might be expected to prevent or delay progression of disease. 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 can therefore be achieved by specifically inhibiting the aromatase enzyme. Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis) that has been shown to be effective in other neoplasms that affect women, such as breast cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Definite diagnosis of based on compatible chest CT and at least one of the following:

1. biopsy or cytology consistent with LAM, or

2. tuberous sclerosis, renal angiomyolipoma, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen, or

3. serum VEGF-D = 800 pg/uL.

• post bronchodilator FEV1 =80% predicted or DLCO =70% predicted or RV=120% predicted
• female and postmenopausal status as defined by one of the following:

1. prior bilateral oophorectomy or bilateral ovarian irradiation, or

2. age greater than 55 years, and no menstrual period for 12 months or longer.

3. age 18-55 years and estradiol level in the postmenopausal range in the absence of current use of progestational agents.

• If still premenopausal, may enter if rendered medically postmenopausal on clinical grounds with the use of gonadotropin releasing hormone (e.g. leuprolide), as long as serum estradiol, FSH, and LH are in the postmenopausal range
• Patients with osteopenia or osteoporosis must be receiving appropriate treatment for their osteoporosis or osteopenia at entry into this study.

Exclusion Criteria:

• Known allergy to letrozole
• Inability to comply with pulmonary function tests or follow up visits.
• Treatment with investigational agents within 30 days
• Hormonal therapy (e.g. estrogen, progestin, LHRH agonists or antagonists, estrogen receptor blockers, estrogen receptor down regulators, aromatase inhibitors) within 30 days month of registration
• Medical or psychiatric conditions that would interfere with the ability to provide informed consent.
• abnormal hematologic and hepatic function as defined by the following at the time of

randomization.:

• Neutrophils < 1500/mm3 and platelets < 100,000/mm3
• Bilirubin < 1.25 X upper limit of normal
• SGPT (ALT) or SGOT (AST) >2.5 X upper limit of normal

Related Conditions & MeSH terms

• Lymphangioleiomyomatosis

Intervention

Drug:
• Letrozole
2.5 mg daily for twelve months
• Placebo
placebo given daily for twelve months

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mayo Clinic	Jacksonville	Florida
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Minor and James	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lu C, Lee HS, Pappas GP, Dilling DF, Burger CD, Shifren A, Veeraraghavan S, Chapman JT, Parambil J, Ruoss SJ, Young LR, Hammes SR, Kopras EJ, Roads T, Krischer JP, McCormack FX; Trial of an Aromatase Inhibitor in Lymphangioleiomyomatosis Group. A Phase II — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month	FEV1 values reported are in liters or milliliters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Higher FEV1 scores indicate better lung function.	12 months
Secondary	Post-bronchodilator FVC	Post-bronchodilator FVC in milliliters	twelve months
Secondary	St George Respiratory Questionnaire	Quality of Life scale for respiratory symptoms. This is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating worse quality of life.	twelve months
Secondary	Serum VEGF-D	VEGF-D values represent serum VEGF-D levels in pg/ml. Higher levels of VEGF-D are associated with Lymphangioleiomyomatosis. A serum VEGF-D greater than 400 pg/ml is a diagnostic biomarker for LAM.	twelve months