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

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT00789828

First received: November 12, 2008

Last updated: March 25, 2013

Last verified: March 2013

History of Changes

Results First Received: March 1, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	Tuberous Sclerosis Subependymal Giant Cell Astrocytoma
Interventions:	Drug: Everolimus Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients in the study were randomized in a 2:1 ratio (Everolimus: Placebo).

Reporting Groups

	Description
Everolimus	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.
Placebo	Matching Placebo was administered orally.

Participant Flow: Overall Study

	Everolimus	Placebo
STARTED	78	39
COMPLETED	2 ^[1]	8
NOT COMPLETED	76	31
Ongoing in Double Blind	76	31

[1]	Completed means discontinued the double-blind treatment period.

Baseline Characteristics

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Reporting Groups

	Description
Everolimus	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.
Placebo	Matching Placebo was administered orally.
Total	Total of all reporting groups

Baseline Measures

	Everolimus	Placebo	Total
Number of Participants [units: participants]	78	39	117
Age [units: years] Mean ± Standard Deviation	10.1 ± 5.9	10.3 ± 7.3	10.2 ± 6.4
Age, Customized [units: Participants]
<3 years	13	7	20
3-18 years	55	26	81
≥18 years	10	6	16
Gender [units: participants]
Female	29	21	50
Male	49	18	67

Outcome Measures

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1. Primary:

Subependymal Giant Cell Astrocytomas (SEGA) Response Rate [ Time Frame: From date of randomization until the earliest date of first documented SEGA progression, date of further anti-SEGA medication (including open-label Everolimus)/surgery or analysis cut-off date (02-Mar-2011) ]

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2. Secondary:

Change From Baseline to Week 24 in Total Seizure Frequency Per 24 Hours From Video EEG as Per Central Reader. [ Time Frame: Baseline, Week 24 ]

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Measure Type	Secondary
Measure Title	Change From Baseline to Week 24 in Total Seizure Frequency Per 24 Hours From Video EEG as Per Central Reader.
Measure Description	The video EEG recordings were sent to a Central Reader for interpretation and recording of seizure frequency/type. Seizure frequency per 24 hours is defined as the number of seizures in the EEG divided by the number of hours in the EEG, multiplied by 24. Seizure frequency was listed as missing if the actual EEG recording duration was <18 hours.
Time Frame	Baseline, Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Full Analysis Set (FAS) consisted of all randomized patients. The analysis was done by using a last observation carried forward approach.

Reporting Groups

	Description
Everolimus	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.
Placebo	Matching Placebo was administered orally.

Measured Values

	Everolimus	Placebo
Number of Participants Analyzed [units: participants]	78	39
Change From Baseline to Week 24 in Total Seizure Frequency Per 24 Hours From Video EEG as Per Central Reader. [units: seizures per 24 hours] Median ( Full Range )	0.0 ( -34.0 to 13.0 )	0.0 ( -15.9 to 14.4 )

No statistical analysis provided for Change From Baseline to Week 24 in Total Seizure Frequency Per 24 Hours From Video EEG as Per Central Reader.

3. Secondary:

Time to SEGA Progression Based on Independent Central Radiology Review [ Time Frame: From date of randomization until the earliest date of first documented SEGA progression, date of further anti-SEGA medication (including open-label Everolimus)/surgery or analysis cut-off date (02-Mar-2011) ]

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4. Secondary:

Skin Lesion Response Rate as Per Investigator Assessment Using the Physician's Global Assessment of Clinical Condition (PGA) [ Time Frame: From date of randomization until the earliest date of first skin lesion progression, date of start of further therapy against skin lesions (including open-label Everolimus) or analysis cut-off date (02-Mar-2011) ]

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5. Secondary:

Change From Baseline in Angiogenesis Biomarkers [ Time Frame: Baseline, Week 4, Week 12, Week 24, Week 36 and Week 48 ]

Results not yet posted. Anticipated Posting Date: 09/2014 Safety Issue: No

6. Secondary:

Changes in Renal Function Assessed Using Creatinine Clearance/Globerular Filtration Rate. [ Time Frame: From start of treatment and assessed on a continuous basis through the duration of the study ]

Results not yet posted. Anticipated Posting Date: 09/2014 Safety Issue: Yes

Serious Adverse Events

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Other Adverse Events

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More Information

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