Trial of Aromatase Inhibition in Lymphangioleiomyomatosis (TRAIL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by University of Cincinnati.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
University of Cincinnati
ClinicalTrials.gov Identifier:
NCT01353209
First received: May 11, 2011
Last updated: June 10, 2011
Last verified: June 2011
  Purpose

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


Condition Intervention Phase
Lymphangioleiomyomatosis
Drug: Letrozole
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Trial of Letrozole in Pulmonary Lymphangioleiomyomatosis With or Without Measurable Tumors or Lymph Nodes

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • The effect on Forced Expiratory Volume in one second [ Time Frame: twelve months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Other measures of pulmonary function [ Time Frame: twelve months ] [ Designated as safety issue: No ]
    FVC, DLCO, TLC,RV, FRC, 6MWT

  • Quality of life measures [ Time Frame: twelve months ] [ Designated as safety issue: No ]
    Quality of Life, dyspnea and fatigue, functional performance

  • Serum VEGF-D [ Time Frame: twelve months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: May 2011
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole Drug: Letrozole
2.5 mg daily for twelve months
Other Name: Femara
Placebo Comparator: Placebo Drug: Placebo
sugar pill given daily for twelve months

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 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 inhibiting the aromatase enzyme.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All patients at least must have a diagnosis of pulmonary lymphangioleiomyomatosis as defined by one of the following:

    • CT chest compatible with LAM and a biopsy or cytology consistent withLAM.
    • CT chest consistent with LAM in the setting of tuberous sclerosis, renal angiomyolipomata, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen , or serum VEGF-D > 800 pg/uL.
  • All patients must have a post bronchodilator FEV1 ≤80% predicted or DLCO ≤70% predicted or RV≥120% predicted
  • All patients must be postmenopausal females as defined by one of the following:

    • Prior bilateral oophorectomy or bilateral ovarian irradiation.
    • If age greater than 55 years, no menstrual period for 12 months or longer.
    • If age 55 years or younger, must have an 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.
  • Patients must have adequate 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) and SGOT (AST) < 2.5 X upper limit of normal

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353209

Contacts
Contact: Francis X McCormack, MD 513-558-4831 frank.mccormack@uc.edu
Contact: Tammy Roads, CRC 513-558-2148 tammy.roads@uc.edu

Locations
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Deborah M Conradi, RN    513-558-0027    deborah.conradi@uc.edu   
Contact: Tammy Roads, CRC    513-558-2148    tammy.roads@uc.edu   
Principal Investigator: Francis X McCormack, MD         
Sub-Investigator: Lisa R Young, MD         
Sponsors and Collaborators
University of Cincinnati
Investigators
Principal Investigator: Francis X McCormack, MD University of Cincinnati
  More Information

No publications provided

Responsible Party: Francis X. McCormack, MD, University of Cincinnati College of Medicine
ClinicalTrials.gov Identifier: NCT01353209     History of Changes
Other Study ID Numbers: 5708
Study First Received: May 11, 2011
Last Updated: June 10, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphangioleiomyomatosis
Immune System Diseases
Immunoproliferative Disorders
Lymphangiomyoma
Lymphatic Diseases
Lymphatic Vessel Tumors
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Perivascular Epithelioid Cell Neoplasms
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014