A Study of Nintedanib for LymphAngioleioMyomatosis (LAM) (LAM)
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|ClinicalTrials.gov Identifier: NCT03062943|
Recruitment Status : Recruiting
First Posted : February 24, 2017
Last Update Posted : August 8, 2019
|Condition or disease||Intervention/treatment||Phase|
|Lymphangioleiomyomatosis||Drug: Nintedanib||Phase 2|
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-associated LAM is proposed.
The objective of the trial is to assess the efficacy and a favorable benefit-risk ratio for nintedanib in the treatment of LAM at the dose of 150 mg bid.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Nintedanib for LymphAngioleioMyomatosis (LAM)|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||October 2020|
Experimental: Nintedanib 150mg BID
nintedanib soft gelatine capsules Dose: 150 mg bid Mode of admin. : Oral Duration of treatment: 1 year Duration of follow-up: 12 months after treatment discontinuation
Other Name: OFEV
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03062943
|Contact: Sergio A Harari, MD||+39 02 85 99 firstname.lastname@example.org|
|Contact: Mara Cattaneo||+39 02 85 99 email@example.com|
|Milan, Italy, 20123|
|Contact: Sergio A Harari, MD +39 02 55 40 4580 firstname.lastname@example.org|
|Contact: Mara Cattaeno +39 02 55 40 4127 email@example.com|
|Principal Investigator: Sergio A Harari, MD|
|Sub-Investigator: Olga Torre, MD|
|Sub-Investigator: Roberto Cassandro, MD|
|Principal Investigator:||Sergio A Harari, MD||MultiMedica - San Giuseppe Hospital|