Vascular Anomalies

This is a 3-part Phase 2 randomized study evaluating the safety and efficacy of the mutant-selective PI3Kα inhibitor, zovegalisib (RLY-2608), in adults and children with PIK3CA Related Overgrowth Spectrum (PROS) and malformations driven by PIK3CA mutation. Part 1 is a dose selection, Part 2 is a basket design with exploratory single-arm cohorts for various subpopulations of participants, and Part 3 is randomized, double-blinded study vs placebo.

Recent studies have demonstrated that growth of vascular malformations can be driven by genetic variants in one of 2 signalling pathways. Targeted drugs specific to these pathways have been developed and shown to be effective in treating cancer. This study will describe the effectiveness of (i) 48 weeks of alpelisib therapy for participants with slow-flow vascular malformations and a gene mutation in one of these signalling pathways (module 1) and (ii) 48 weeks of mirdametinib therapy for participants with fast-flow vascular malformations and a gene mutations in the other signalling pathway (module 2).

The goal of this observational study is to create a single macro registry system with data collection on common clinical features, grouping the different rare diseases (RD). Moreover, the specific goals are to generate an alert system for possible cases of RD with data from the electronic medical record, to describe the occurrence of RD in the evaluated population, to characterize the population, to describe patterns of diagnosis and treatment of RD present at the time, and to explore patient-reported outcomes.

Vascular Anomalies (VA) are areas of disorganized blood vessel tissue that can appear as lumps or bumps under the skin. Sometimes they can cause you discomfort, or you may not like how they look. One option for treatment is to place a needle through the skin into the VA and inject medicines called sclerosants that can cause them to shrink. This treatment is called sclerotherapy and is the standard of care. While sclerotherapy is safe and effective, other alternatives for treatment exist, such as using heat. Just like with sclerotherapy, a small needle is inserted through the skin into the VA while the doctor watches it using imaging techniques. Once the needle tip is in the right spot, the needle tip delivers heat energy to the VA, causing it to shrink. We believe that using heat to treat VAs may be safer and more effective than using sclerotherapy, and we are asking for your participation in this study to help us determine whether that is correct. You are being given the option of using heat instead of sclerosant medicines to treat your VA. Regardless of whether you choose targeted heat or sclerosant medicine injection for your treatment, all procedures will be performed under sedation with an anesthesiologist, and you will continue to have appointments with the vascular anomalies clinic after your procedure. The risks to you if you decide to use heat for treatment of your vascular anomaly are similar to injecting sclerosant medicines, which includes bleeding, infection, and damage to nearby structures. There is also the additional risk of heating the skin and causing a burn, but the risk of this is low. Benefits of using heat instead of sclerosant medicine include avoiding sclerosant medicine side effects. Possible benefits include more effective treatment of your vascular anomaly than could be achieved with traditional sclerotherapy. Participation is entirely voluntary, and if you decide not to use heat for treatment of your VA, you are free to discuss with your doctor alternative treatments like sclerotherapy.