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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00789828




Registration number
NCT00789828
Ethics application status
Date submitted
12/11/2008
Date registered
13/11/2008
Date last updated
3/02/2016

Titles & IDs
Public title
Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
Scientific title
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)
Secondary ID [1] 0 0
2007-006997-27
Secondary ID [2] 0 0
CRAD001M2301
Universal Trial Number (UTN)
Trial acronym
EXIST-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberous Sclerosis 0 0
Subependymal Giant Cell Astrocytoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - Placebo

Experimental: 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 comparator: Placebo - Matching Placebo administered orally.


Treatment: Drugs: Everolimus
Everolimus was formulated as tablets of 1.0-mg strength and was blisterpacked under aluminum foil in units of 10 tablets.

Treatment: Drugs: Placebo
Placebo was provided as a matching tablet and was blisterpacked under aluminum foil in units of 10.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
Timepoint [1] 0 0
End of core period (Week 48), and end of extension period (up to 4 years)
Secondary outcome [1] 0 0
Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Time to SEGA Progression
Timepoint [2] 0 0
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Secondary outcome [3] 0 0
Time to SEGA Response
Timepoint [3] 0 0
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Secondary outcome [4] 0 0
Duration of SEGA Response
Timepoint [4] 0 0
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Secondary outcome [5] 0 0
Time to SEGA Worsening
Timepoint [5] 0 0
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Secondary outcome [6] 0 0
Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score
Timepoint [6] 0 0
End of core period (Week 48), and end of extension period (up to 4 years)
Secondary outcome [7] 0 0
Duration of Skin Lesion Response in Everolimus Treated Participants
Timepoint [7] 0 0
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Secondary outcome [8] 0 0
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose
Timepoint [8] 0 0
2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240
Secondary outcome [9] 0 0
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose
Timepoint [9] 0 0
24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240
Secondary outcome [10] 0 0
Percentage of Participants With Renal Impairment During Core Period
Timepoint [10] 0 0
Day 1 up to 28 days after end of treatment (Core period)

Eligibility
Key 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
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
117
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment postcode(s) [1] 0 0
2130 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussel
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Italy
State/province [16] 0 0
GE
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
Netherlands
State/province [18] 0 0
Utrecht
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
Russian Federation
State/province [20] 0 0
Moscow
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticlas
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00789828