Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 3:43 PM
Ignite Modification Date:
2025-12-24 @ 3:43 PM
NCT ID:
NCT03290092
Brief Summary:
Segmental overgrowth disorders are rare conditions characterised by abnormal growth which is usually asymmetric and confined to discrete parts of the body. We and others have identified mosaic activating mutations in the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K; encoded by the PIK3CA gene) in a subset of overgrowth disorders. The PI3K-AKT-mTOR is a critical signalling pathway, which regulates cellular growth, proliferation and survival. Activating mutations in PIK3CA lead to increased activation of the PI3K-AKT-mTORC1 axis, which in turn promotes excessive growth in affected tissue.
The PIK3CA-related overgrowth spectrum is wide, and depends upon the timing of the founder mutation in embryogenesis, and potentially upon the exact mutation. Clinical presentation ranges from isolated enlargement of a digit, to extensive overgrowth of limbs, abdomen and in some cases the brain, and may be accompanied by vascular or lymphatic malformations. Associated morbidity can be profound, with functional impairment, debilitating haemorrhages and thromboses, coupled with neurological sequelae and, in some cases, death. At present, serial debulking surgery is the only available therapeutic option.
The identification of gain-of-function mutations in PI3K has raised the possibility of treatment with drugs that inhibit PIK3CA (the p110 alpha catalytic subunit of PI3K). Taselisib is a selective inhibitor of class I PI3Ks and has direct inhibitory activity of the p110α isoform with a Kiapp value of 0.29 nmol/l.
Study:
NCT03290092
Study Brief:
Protocol Section:
NCT03290092