Clinical trial · Interventional
Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
A Randomized, Double-blind, Placebo-controlled Study of Everolimus in the Treatment of Patients With Subependymal Giant Cell Astrocytomas (SEGA) Associated With Tuberous Sclerosis Complex (TSC)
NCT00789828CI-TRIAL-00020783EXIST-1completedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Subependymal Giant Cell Astrocytoma | Subependymal Giant Cell Astrocytoma | ONTOLOGY_EXACT | 0.90 |
| Tuberous Sclerosis | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Everolimus | Drug | Everolimus | ALIAS |
| Placebo | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Everolimus
- description
- Everolimus was administered orally at a starting dose of 4.5mg/m\^2 daily and subsequently titrated to attain whole blood trough concentration of 5 to 15 ng/mL. Dose adjustments were permitted based on safety and whole blood trough concentrations.
- interventionNames
- Drug: Everolimus
- type
- PLACEBO_COMPARATOR
- label
- Placebo
- description
- Matching Placebo administered orally.
- interventionNames
- Drug: Placebo
Primary outcomes (1)
- measure
- Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
Eligibility
Eligibility (as posted)
- Sex
- All
Show eligibility criteria text
Inclusion Criteria: * All Ages * Definite diagnosis of Tuberous Sclerosis according to the modified Gomez criteria * At least one Subependymal Giant Cell Astrocytoma of at least 1 cm in diameter * Evidence of SEGA worsening as compared to prior MRI scans * Females of child bearing potential must use birth control * Written informed consent Exclusion Criteria: * SEGA related surgery is likely to be required in the opinion of the investigator * Recent heart attack, cardiac related chest pain or stroke * Severely impaired lung function * Severe liver dysfunction * Severe kidney dysfunction * Pregnancy or breast feeding * Current infection * History of organ transplant * Surgery within two months prior to study enrollment * Prior therapy with a medication in the same class as Everolimus * Uncontrolled high cholesterol * Uncontrolled diabetes * HIV * Patients with metal implants thus prohibiting MRI evaluations Other protocol-defined inclusion/exclusion criteria may apply
References
Publications (9)
- DERIVEDBissler JJ, Budde K, Sauter M, Franz DN, Zonnenberg BA, Frost MD, Belousova E, Berkowitz N, Ridolfi A, Christopher Kingswood J. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019 Jun 1;34(6):1000-1008. doi: 10.1093/ndt/gfy132. PMID 30053159
- DERIVEDSparagana S, Franz DN, Krueger DA, Bissler JJ, Berkowitz N, Burock K, Kingswood JC. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. PLoS One. 2017 Oct 12;12(10):e0186235. doi: 10.1371/journal.pone.0186235. eCollection 2017. PMID 29023494
- DERIVEDFranz DN, Belousova E, Sparagana S, Bebin EM, Frost MD, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Berkowitz N, Niolat J, Jozwiak S. Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study. PLoS One. 2016 Jun 28;11(6):e0158476. doi: 10.1371/journal.pone.0158476. eCollection 2016. PMID 27351628
- DERIVEDJozwiak S, Kotulska K, Berkowitz N, Brechenmacher T, Franz DN. Safety of Everolimus in Patients Younger than 3 Years of Age: Results from EXIST-1, a Randomized, Controlled Clinical Trial. J Pediatr. 2016 May;172:151-155.e1. doi: 10.1016/j.jpeds.2016.01.027. Epub 2016 Feb 6. PMID 26858193
- DERIVEDGoyer I, Dahdah N, Major P. Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex. Pediatr Neurol. 2015 Apr;52(4):450-3. doi: 10.1016/j.pediatrneurol.2015.01.004. Epub 2015 Jan 14. PMID 25682485
- DERIVEDFranz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Berkowitz N, Anak O, Niolat J, Jozwiak S. Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. Lancet Oncol. 2014 Dec;15(13):1513-1520. doi: 10.1016/S1470-2045(14)70489-9. Epub 2014 Nov 10.