CBYL719P12201: alpelisib in patients with lymphatic malformations with PIK3CA mutation
Research type
Research Study
Full title
A two-stage double-blind, randomised, placebo-controlled study to assess the efficacy, safety and pharmacokinetics of alpelisib in paediatric and adult patients with lymphatic malformations associated with a PIK3CA mutation
IRAS ID
1011403
Contact name
Fiona Morris
Contact email
Sponsor organisation
Novartis Pharmaceuticals UK Ltd.
Clinicaltrials.gov Identifier
Research summary
The purpose of this trial is to learn if the trial drug, alpelisib (BYL719), works in children and adults who have lymphatic malformations (also called LyMs) that are associated with a change (called a mutation) in the instructions (DNA) that make up the PIK3CA gene. LyMs consist of fluid-filled cysts of various sizes and in various locations, and they cause many symptoms that can affect quality of life. LyMs are currently treated with surgery, injecting liquid/ foam into the LyM (sclerotherapy), or blocking vessels to reduce flow (embolisation). There is no approved drug treatment for LyMs.
Mutations in the PIK3CA gene are detected in 75-90% of patients with LyMs, which can cause the PI3K signalling pathway to become overactive in affected cells. Alpelisib is a drug designed to block this overly active pathway.
This is a two-stage study where participants are treated with alpelisib for approximately 5 years. The purpose of Stage 1 is to select the most appropriate dose of alpelisib for the treatment of LyMs in different age groups (Group 1: 18 years and older), Group 2: 6-17 years). If during Stage 1 alpelisib shows sufficient efficacy and potential benefit in at least one group, Stage 2 will be open to enrol adult participants in Group 3 and/or paediatric participants in Group 4 (6-17 years). This is the point at which the UK will join the study. The main purpose of Stage 2 is to confirm efficacy of the selected dose in reducing LyM volume (up to 3 lesions) and improving symptoms of LyMs in Group 3 and/or 4. If Group 4 is opened in Stage 2, an exploratory Group 5 will also recruit participants 0-5 years of age. The main purpose of Group 5 is to assess safety and response over time of alpelisib in the youngest participants after having established safety and efficacy of alpelisib in Group 2.
In addition, this study is designed to learn more about the safety of alpelisib and how the amount of drug changes in blood over time in Stage 1 and 2.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
25/NE/0171
Date of REC Opinion
5 Nov 2025
REC opinion
Further Information Favourable Opinion