Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
NCT ID: NCT00789828
Last Updated: 2016-02-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
117 participants
INTERVENTIONAL
2009-08-31
2014-10-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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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.
Everolimus
Everolimus was formulated as tablets of 1.0-mg strength and was blisterpacked under aluminum foil in units of 10 tablets.
Placebo
Matching Placebo administered orally.
Placebo
Placebo was provided as a matching tablet and was blisterpacked under aluminum foil in units of 10.
Interventions
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Everolimus
Everolimus was formulated as tablets of 1.0-mg strength and was blisterpacked under aluminum foil in units of 10 tablets.
Placebo
Placebo was provided as a matching tablet and was blisterpacked under aluminum foil in units of 10.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticlas
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Barrow Tuberous Sclerosis Center
Phoenix, Arizona, United States
University of California at Los Angeles
Los Angeles, California, United States
Children's Hospital Oakland Hematology/Oncology Dept
Oakland, California, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
University of CHicago Comer Children's Hospital
Chicago, Illinois, United States
Massachusetts General Hospital Mass General
Boston, Massachusetts, United States
Children's Hospital Boston SC-1
Boston, Massachusetts, United States
Minnesota Epilepsy Group - PA
Saint Paul, Minnesota, United States
Cincinnati Children's Hospital Medical Center Cincinnati Children's Hosp
Cincinnati, Ohio, United States
Texas Scottish Rite Hospital for Children
Dallas, Texas, United States
Children's Regional Outpatients Center SC
Fairfax, Virginia, United States
Novartis Investigative Site
Randwick, New South Wales, Australia
Novartis Investigative Site
Brussels, , Belgium
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Québec, , Canada
Novartis Investigative Site
Berlin, , Germany
Novartis Investigative Site
Heidelberg, , Germany
Novartis Investigative Site
Genova, GE, Italy
Novartis Investigative Site
Roma, , Italy
Novartis Investigative Site
Utrecht, Netherlands, Netherlands
Novartis Investigative Site
Warsaw, , Poland
Novartis Investigative Site
Moscow, , Russia
Novartis Investigative Site
Bristol, , United Kingdom
Countries
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References
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Bissler 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.
Sparagana 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.
Franz 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.
Jozwiak 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.
Goyer 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.
Franz 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.
Kingswood JC, Jozwiak S, Belousova ED, Frost MD, Kuperman RA, Bebin EM, Korf BR, Flamini JR, Kohrman MH, Sparagana SP, Wu JY, Brechenmacher T, Stein K, Berkowitz N, Bissler JJ, Franz DN. The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1. Nephrol Dial Transplant. 2014 Jun;29(6):1203-10. doi: 10.1093/ndt/gfu013. Epub 2014 Apr 11.
Kotulska K, Borkowska J, Jozwiak S. Possible prevention of tuberous sclerosis complex lesions. Pediatrics. 2013 Jul;132(1):e239-42. doi: 10.1542/peds.2012-3607. Epub 2013 Jun 3.
Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, Curatolo P, de Vries PJ, Whittemore VH, Thiele EA, Ford JP, Shah G, Cauwel H, Lebwohl D, Sahmoud T, Jozwiak S. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013 Jan 12;381(9861):125-32. doi: 10.1016/S0140-6736(12)61134-9. Epub 2012 Nov 14.
Related Links
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Visit EXIST-1 NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.
Other Identifiers
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2007-006997-27
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CRAD001M2301
Identifier Type: -
Identifier Source: org_study_id
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