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

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ClinicalTrials.gov Identifier: NCT00789828
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : May 1, 2012
Last Update Posted : February 3, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Tuberous Sclerosis
Subependymal Giant Cell Astrocytoma
Interventions: Drug: Everolimus
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 24 centers in 10 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 117 participants were enrolled and randomized into the core period. Only 111 participants completing the core period, continued in the open-label extension period of the study.

Reporting Groups
  Description
Everolimus Participants received oral dose of everolimus 4.5 milligram/square meter (mg/m^2) daily as an initial starting dose to attain the whole blood trough concentrations in range of 5-15 nanogram/millilitre (ng/mL). Dose adjustments were permitted based on safety and whole blood trough concentrations.
Placebo Participants received oral dose of placebo matching to everolimus daily.

Participant Flow for 2 periods

 Period 1:   Core Period (48 Weeks)
    Everolimus   Placebo
STARTED   78   39 
COMPLETED   78   33 
NOT COMPLETED   0   6 
Administrative problems                0                1 
Withdrawal by Subject                0                4 
Lost to Follow-up                0                1 

Period 2:   Open-label Extension Period (4 Years)
    Everolimus   Placebo
STARTED   111 [1]   0 [2] 
COMPLETED   82   0 
NOT COMPLETED   29   0 
Adverse Event                10                0 
Withdrawal by Subject                6                0 
Lost to Follow-up                3                0 
Administrative problems                7                0 
Death                1                0 
Disease progression                1                0 
New treatment for indication under study                1                0 
[1] Of 117 participants only 111 completed the core period and continued in the extension period
[2] No participant received placebo.



  Baseline Characteristics

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.
No text entered.

Reporting Groups
  Description
Everolimus (Core Period) Participants received oral dose of everolimus 4.5 mg/m^2 daily as an initial starting dose to attain the whole blood trough concentrations in range of 5-15 ng/mL. Dose adjustments were permitted based on safety and whole blood trough concentrations.
Placebo (Core Period) Participants received oral dose of placebo matching to everolimus daily.
Total Total of all reporting groups

Baseline Measures
   Everolimus (Core Period)   Placebo (Core Period)   Total 
Overall Participants Analyzed 
[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

1.  Primary:   Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response   [ Time Frame: End of core period (Week 48), and end of extension period (up to 4 years) ]
  Show Outcome Measure 1

2.  Secondary:   Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period   [ Time Frame: Baseline (Core period) to Week 24 (Core period), Baseline (Extension period, Week 24 post-core baseline) to Week 24 (Extension period, Week 48 post-core baseline) ]
  Show Outcome Measure 2

3.  Secondary:   Time to SEGA Progression   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]
  Show Outcome Measure 3

4.  Secondary:   Time to SEGA Response   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]
  Show Outcome Measure 4

5.  Secondary:   Duration of SEGA Response   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]
  Show Outcome Measure 5

6.  Secondary:   Time to SEGA Worsening   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]
  Show Outcome Measure 6

7.  Secondary:   Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score   [ Time Frame: End of core period (Week 48), and end of extension period (up to 4 years) ]
  Show Outcome Measure 7

8.  Secondary:   Duration of Skin Lesion Response in Everolimus Treated Participants   [ Time Frame: Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) ]
  Show Outcome Measure 8

9.  Secondary:   Everolimus Blood Concentration (C2h) at 2 Hours Post Dose   [ Time Frame: 2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240 ]
  Show Outcome Measure 9

10.  Secondary:   Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose   [ Time Frame: 24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240 ]
  Show Outcome Measure 10

11.  Secondary:   Percentage of Participants With Renal Impairment During Core Period   [ Time Frame: Day 1 up to 28 days after end of treatment (Core period) ]
  Show Outcome Measure 11


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information