Clinical Trial: Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Safety and Efficacy of Saracatinib In Subjects With Lymphangioleiomyomatosis

Brief Summary: This study is being done to determine if there is a potential benefit of saracatinib in LAM subjects. Based on the information of this trial, additional clinical development trials will be needed. The study will also test the tolerability of 125 mg of saracatinib given once daily over a 9 month period.

Detailed Summary:

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in tuberous sclerosis complex 1 (TSC1) or TSC2 tumor suppressor genes. TSC is characterized by tumors in a wide range of tissues, seizures, mental retardation, autism, and organ failure. Lymphangioleiomyomatosis (LAM), the major pulmonary manifestation in women with TSC, is a progressive lung disease characterized by infiltration of atypical smooth muscle like cells (TSC-/- LAM cells) and formation of parenchymal cysts. Sporadic LAM can develop in women who do not meet the criteria for the diagnosis of TSC, owing to somatic mutations in the TSC2 gene.

The long term goal of this research is to devise novel therapeutic strategies for patients with LAM. The observed behavior of LAM cells with respect to their infiltrative growth pattern, metastatic potential, and altered cell differentiation is reminiscent of cells undergoing epithelial-mesenchymal transition (EMT). Src kinases are key regulators of cellular proliferation, motility, invasiveness and EMT. Recent results have shown that autophagy promotes degradation of active Src. Thereby, decreased autophagy due to mTOR activation known to occur in LAM cells, may play a significant role in accumulation of active Src in these cells. Src suppresses transcription of E-cadherin by upregulating its transcriptional repressors. The preliminary data reveal an increase in active Src in lung tissues of patients with LAM as well as in cultured TSC2-/- cells. Further, in TSC2-/- cells, E-cadherin is considerably reduced and does not localize to the plasma membrane, as it does in wild-type cells.

The focus of this study is to examine if Src inhibition represents a potential therapeutic strategy in LAM. It is proposed that Src activation in TSC2-/- cells results in the reduction of E-cadherin, loss of ce
Sponsor: Baylor College of Medicine

Current Primary Outcome: FEV1 [ Time Frame: 9 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Angiomyolipoma measured volumetrically on MRI [ Time Frame: 12 months ]
  • Lung Cyst size measured on chest CT [ Time Frame: 9 months ]
  • VEGF-D serum levels [ Time Frame: 12 months ]


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: March 31, 2016
Date Started: April 2016
Date Completion: December 2017
Last Updated: November 28, 2016
Last Verified: November 2016