Letrozole for Lymphangioleiomyomatosis

NCT01353209 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 5708
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 9

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

Conditions

Lymphangioleiomyomatosis

Keywords

Lymphangiomyomatosis; Postmenopausal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Post-bronchodilator FVC

  twelve months

• St George Respiratory Questionnaire

  twelve months

• Serum VEGF-D

  twelve months

Study Arms (2)

Letrozole

EXPERIMENTAL

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

Drug: Letrozole

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Letrozole DRUG

2.5 mg daily for twelve months

Also known as: Femara

Letrozole

Placebo DRUG

placebo given daily for twelve months

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Definite diagnosis of based on compatible chest CT and at least one of the following:
• biopsy or cytology consistent with LAM, or
• tuberous sclerosis, renal angiomyolipoma, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen, or
• 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:
• prior bilateral oophorectomy or bilateral ovarian irradiation, or
• age greater than 55 years, and no menstrual period for 12 months or longer.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cincinnati: lead
• United States Department of Defense: collaborator

Study Sites (9)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Minor and James

Seattle, Washington, 98122, United States

Location

Related 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 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.

  PMID: 28570161 RESULT

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Letrozole; Sugars

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Limitations and Caveats

Under enrollment. Post menopause not originally assessed by estradiol levels. Small sample sizes led to some imbalances in baseline parameters, such as VEGF-D levels and bronchodilator responsiveness, which could have biased outcomes.

Results Point of Contact

• Title: Susan McMahan, Clinical Research Manager
• Organization: University of Cincinnati

Susan.mcmahan@uc.edu

513-558-4831

Study Officials

• Francis X McCormack, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Pulmonary, Critical Care and Sleep Medicine

Study Record Dates

• First Submitted: May 11, 2011
• First Posted: May 12, 2011
• Study Start: May 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: April 17, 2024
• Results First Posted: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: immediately, indefinitely
• Access Criteria: Email the PI: mccormfx@ucmail.uc.edu

Locations

US (9)