Phase 3 N=117 Randomized Quadruple-blind Treatment

Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)

Tuberous Sclerosis · Subependymal Giant Cell Astrocytoma

Bottom Line

View on ClinicalTrials.gov: NCT00789828 ↗

Enrolled (actual)

117

Serious AEs

45.3%

Results posted

May 2012

Primary outcome: Primary: Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response — 34.6; 0.0; 57.7 Percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Everolimus (Drug); Placebo (Drug)
Age: Pediatric, Adult, Older Adult
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: Mar 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response	34.6; 0.0; 57.7	—
SECONDARY Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period	-1.24; -0.24; -6.07	—
SECONDARY Time to SEGA Progression	NA; NA; NA	—
SECONDARY Time to SEGA Response	2.99; 5.32	—
SECONDARY Duration of SEGA Response	NA; NA	—
SECONDARY Time to SEGA Worsening	NA; NA; 55.72	—
SECONDARY Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score	41.7; 10.5; 58.1	—
SECONDARY Duration of Skin Lesion Response in Everolimus Treated Participants	NA; NA	—
SECONDARY Everolimus Blood Concentration (C2h) at 2 Hours Post Dose	27.52; 27.74; 38.7; 39.25; 23.2; 49.73	—
SECONDARY Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose	5.8; 6.09; 6.59; 6.86; 7.28; 7.07	—
SECONDARY Percentage of Participants With Renal Impairment During Core Period	0; 0; 3.8; 0; 96.2; 100	—

Summary

This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00789828). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.