Clinical Trial: A Study of Nintedanib for LymphAngioleioMyomatosis (LAM)

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

Official Title: A Pilot Study of Nintedanib for LymphAngioleioMyomatosis (LAM)

Brief Summary: This trial is conducted locally. The aim of this trial is assess the efficacy and a favorable benefit-risk ratio for nintedanib in the treatment of LAM at the dose of 150 mg bid

Detailed Summary:

There is a high unmet medical need for efficacious and safe treatment of LAM, to halt lung function decline, improve patient-reported outcome, reduce size of angiomyolipomas and ultimately decrease mortality. Guidelines recommend participation in research trials if possible.

To date, therapeutic options include mTOR inhibitors sirolimus and everolimus. Among these, sirolimus, has been approved by FDA based on a clinical trial which showed a stabilization of lung function expressed as FEV1 during the 12 month treatment period. Thus the stabilization of lung function appears to require continuous exposure to the drug. Sirolimus is associated with an increased frequency of adverse events like mucositis, gastrointestinal events, hypercholesterolemia, acneiform rash, and swelling in the lower extremities.

Nintedanib was shown to dose-dependently inhibit PDGFR phosphorylation and subsequent signaling via protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 in lung tissue from mice. Akt and ERK 2 can both phosphorylate tuberin resulting in inactivation of hamartin-tuberin complex and consequent activation of mTOR .

It has been demonstrated that platelet-derived growth factor β receptor (PDGFRβ) is present and active in human and murine TSC lesions. Thus, an inhibition of PDGFR may be effective in LAM. Moreover, the inhibition of VEGF, PDGF and FGF signaling pathways reduces tumor angiogenesis in lung. As angiogenesis and lymphangiogenesis are mechanisms involved in dissemination of LAM cells, potential inhibition of angiogenesis by nintedanib may contribute to prevent disease progression in LAM.

Therefore, a non-randomized, efficacy, safety, and tolerability trial of nintedanib in sporadic and TSC-as
Sponsor: IRCCS Multimedica

Current Primary Outcome: FEV1 rate decline [ Time Frame: up to 12 months ]

Change in FEV1 (Force Expiratory Volume in 1 second) in milliliters per month. The FEV1 slope will be calculated at baseline and at 3, 6, 9 and up to 12 months during the treatment phase.


Original Primary Outcome: Same as current

Current Secondary Outcome: Safety and Tolerability in terms of AEs, particularly for liver function and level of hepatic enzymes. [ Time Frame: up to 12 months ]

Safety and Tolerability profile: assessment of any AEs, increased levels of hepatic enzymes, kidney and gastrointestinal tract functionality. All the adverse events will be classified depending of time of occurency: treatment emergent adverse events if they occur after the first dose of study medication up to a period of 28 days or alternatively as either to the screening or post treatment, or post study phase, as appropriate.


Original Secondary Outcome: Same as current

Information By: IRCCS Multimedica

Dates:
Date Received: October 7, 2016
Date Started: October 2016
Date Completion: October 2020
Last Updated: February 20, 2017
Last Verified: October 2016