Letrozole for Lymphangioleiomyomatosis

NCT ID: NCT01353209

Last Updated: 2024-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-09-30

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 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.

Conditions

Lymphangioleiomyomatosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Letrozole

Patients are placed on letrozole, 1 tablet (2.5 mg) daily for one year

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

2.5 mg daily for twelve months

Placebo

Patients are placed on placebo, 1 tablet daily for one year

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo given daily for twelve months

Interventions

Letrozole

2.5 mg daily for twelve months

Intervention Type: DRUG

Placebo

placebo given daily for twelve months

Intervention Type: DRUG

Other Intervention Names

Femara; sugar pill

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Francis McCormack

Professor and Director, Pulmonary, Critical Care and Sleep Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francis X McCormack, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

Stanford University Medical Center

Stanford, California, United States

Mayo Clinic

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Loyola University Medical Center

Maywood, Illinois, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Minor and James

Seattle, Washington, United States

Countries

United States

References

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 Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2017 Jun;14(6):919-928. doi: 10.1513/AnnalsATS.201610-824OC.

Reference Type: RESULT

PMID: 28570161 (View on PubMed)

Other Identifiers

5708

Identifier Type: -

Identifier Source: org_study_id