An open label phase II study of Sirolismus in patients with segmental overgrowth syndrome (SIPA-SOS)

• Applicant: Dr. Friedrich Kapp, since 9/2019
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 403830062

Segmental overgrowth syndromes are rare diseases presenting soft tissue lesions and skeletal growth disturbances as well as vascular malformations at birth or early in lifetime and continuous progression. In consequence, patients can suffer from severe functional and esthetic troubles leading to reduced life quality and neuropsychological problems. Until recently, only surgical procedures, sclerotherapy/embolization or conservative measures with orthopedic utilities and supportive care could be offered. Lately, several somatic mutations have been identified in tissues of these patients all of them affecting molecules of the mTOR signaling pathway, such as f.e. PI3KCA mutations in CLOVE syndrome, AKT1 in Proteus syndrome as well as PTEN germline mutations in the Cowden or SOLAMEN syndrome. These data and first case reports on successful use of the mTOR inhibitor Sirolimus give hope for cure of this condition. In this phase II trial, patients with a segmental overgrowth syndrome showing at least one progressive lesion will be enrolled in a 6 months observation period (control) followed by 6 months treatment with Sirolimus. The primary outcome will be change in size of the defined lesion in MRIs performed at study entry, at start and the end of the treatment period. Furthermore, disfigurement, changes in quality of life and in neuropsychological tests will be studied as well as biomarkers and pharmacodynamics of the Sirolimus therapy complemented by safety of the therapy. The result could support the first targeted medical therapy in segmental overgrowth syndromes.

• DFG Programme: Clinical Trials
• Co-Investigator: Professorin Dr. Charlotte Niemeyer
• Ehemaliger Antragsteller: Professor Dr. Jochen Rößler, until 9/2019