Neuropediatrics 2012; 43 - FV12_03
DOI: 10.1055/s-0032-1307057

An opel-label, multi-center, expanded access study of RAD001 (Everolimus) in patients with TSC SEGA

C Hertzberg 1, B Wilken 2, M Nathrath 2, A Gnekow 3, J Penzien 3, G Janßen 4, M Karenfort 4, P Hernáiz Driever 5, A Rübel 6, O Witt 7
  • 1Vivantes Klinikum Neukölln, Berlin, Germany
  • 2Klinikum Kassel GmbH, Kassel, Germany
  • 3Klinikum Augsburg, Augsburg, Germany
  • 4Universitätsklinikum Düsseldorf, Düsseldorf, Germany
  • 5Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany
  • 6Novartis Pharma GmbH, Nürnberg, Germany
  • 7DKFZ & Universitätsklinikum Heidelberg, Heidelberg, Germany

Aims: TSC is a rare disease that manifests as benign tumor-like lesions, called hamartomas, in multiple organs, including the brain, skin, eyes, heart, lungs, and kidneys. Approximately 85% of children and adolescents with TSC experience manifestations in the central nervous system (CNS), such as subependymal giant-cell astrocytomas (SEGAs), subependymal nodules (SEN), epilepsy and neurocognitive deficits.

SEGA lesions are usually located near the foramen of Monro. Typically they are slowly growing lesions that are clinically unapparent until they reach sufficient size to produce ventricular obstruction and hydrocephalus.

This European Phase IIIb trial was designed to provide Everolimus to patients who are without satisfactory nonsurgical treatment alternatives, until the product is commercially available.

Methods: Patients of age 3 years or older who have been diagnosed with TSC associated SEGA were allowed to enter this study. Everolimus was given daily at starting doses of 3mg/m2 orally (titrated to achieve target trough concentrations of 5–15ng/mL). MRI-based SEGA assessments were performed at baseline, 3 and 6 months, and every 6 months thereafter.

Results: In Germany a total of 16 patients on 8 sites participated on the trial. At each site a multidisciplinary team of pediatric neurologists and pediatric oncologists took care for the patients. Final analysis about safety and investigator's best overall response rate will be done at European level after the trial has finished in all participating countries. Therefore German data will be shown at congress.

Conclusion: Previous phase III studies demonstrated the efficacy of Everolimus to reduce SEGA volume and AML volume in TSC patients. Additional trials (phase II) revealed that Everolimus may have the potential to reduce seizures and improve cognition, as reported by caregivers. Therefore Everolimus is a treatment option for patients with TSC SEGA. The interdisciplinary approach between pediatric oncologists and pediatric neurologists is important to have an optimal medical treatment situation in TSC.

TSC - SEGA - Everolimus - interdisciplinary approach