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)
Primary Purpose
Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Everolimus
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Tuberous Sclerosis focused on measuring SEGA, Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma, mTOR, RAD001, Mamalian Target Rapamycin, Everolimus, TSC
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
Sites / Locations
- University of Alabama at Birmingham
- Barrow Tuberous Sclerosis Center
- University of California at Los Angeles
- Children's Hospital Oakland Hematology/Oncology Dept
- Children's Healthcare of Atlanta
- University of CHicago Comer Children's Hospital
- Massachusetts General Hospital Mass General
- Children's Hospital Boston SC-1
- Minnesota Epilepsy Group - PA
- Cincinnati Children's Hospital Medical Center Cincinnati Children's Hosp
- Texas Scottish Rite Hospital for Children
- Children's Regional Outpatients Center SC
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Everolimus
Placebo
Arm Description
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.
Matching Placebo administered orally.
Outcomes
Primary Outcome Measures
Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
Participants were assessed for SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilized to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.
Secondary Outcome Measures
Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period
Seizure frequency per 24 hours was defined as the number of seizures in the electroencephalography (EEG) divided by the number of hours in the EEG, multiplied by 24. Seizure frequency was evaluated using a 24-hour video-EEG. Seizure frequency was listed as missing if the actual EEG recording duration was < 18 hours.
Time to SEGA Progression
Time to SEGA progression was defined as time between randomisation to time to first SEGA progression. SEGA progression was defined as either one or more of the following criteria: 1. increase from nadir of ≥ 25% in SEGA volume to a value greater than baseline SEGA volume (where SEGA volume is the sum of the volumes of all target SEGA lesions identified at baseline, and nadir is the lowest SEGA volume obtained for the participant previously in the trial), 2. unequivocal worsening of non-target SEGA lesions, 3. appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, 4. new or worsening hydrocephalus. The median TTSP based on central radiology review was not reached in any treatment arms; Only 6 events of SEGA progressions were observed in the placebo group of core period.
Time to SEGA Response
Participants were assessed for time to SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilised to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.
Duration of SEGA Response
Duration of SEGA response was defined as time from the date of the first documented SEGA response until the date of the first documented SEGA progression. Duration of SEGA response was evaluated only for participants who achieved a SEGA response. The time to SEGA progression was censored if SEGA progression was not observed before the first to occur out of (i) analysis cut-off date (ii) the date when systemic anti-SEGA medication is started, (iii) the date of a SEGA-related surgery or (iv) the date of death. Since, no case of SEGA progression was observed in core study which resulted in censored duration of SEGA response. Only 5 SEGA responders experienced a SEGA progression in extension period.
Time to SEGA Worsening
Time to SEGA worsening was defined as the time from the start of everolimus to date of the first SEGA worsening. SEGA worsening was defined as either; increase from nadir of ≥ 25% in SEGA volume or unequivocal worsening of non-target SEGA lesions, or appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, or new or worsening hydrocephalus. The median value was not reached in either treatment arm of core period as SEGA worsening was observed in less participants (everolimus - 7 and placebo - 8).
Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score
Skin lesions included hypomelanotic macules, the shagreen patch, periungual or subungual fibromas, facial angiofibromas and/or forehead plaques. Response was evaluated using the Physician's Global Assessment of Clinical Condition (PGA) on a 7-point scale: Grade 0 = complete clinical response, indicated absence of disease, Grade 1, 2, and 3 = partial response, indicated improvements of ≥ 50% but < 100%, Grade 4, 5 = stable disease, indicated some or no improvements of 25% - < 50% and 6 = progressive disease, indicated worse than at baseline evaluation by > 25%. Response rate was determined for participants with ≥ 1 skin lesion at baseline, defined as the percentage of participants with overall status as complete clinical response or partial response.
Duration of Skin Lesion Response in Everolimus Treated Participants
Duration of skin lesion response was defined as the time from the first skin lesion response until the first skin lesion progression, defined as worsening of lesion by > 25% or more from baseline.
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose
The participants were assessed for everolimus blood concentration at 2 hours time point after dose administration on the same day, if the participant did not vomit between previous dose and blood sample collection. Tandem liquid chromatography-mass spectrometry method was used for evaluation. C2h values were categorized as < 20 ng/mL, 20-50 ng/mL, and > 50 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose
The participants were assessed for everolimus trough concentration (Cmin) at 24 hours time point after previous dose administration, at a steady state following 5 days of consistent dosing, if the participant did not vomit within 4 hours of previous dose. Tandem liquid chromatography-mass spectrometry method was used for evaluation. Cmin values were categorized as <5 ng/mL, 5-10 ng/mL, and >10 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.
Percentage of Participants With Renal Impairment During Core Period
Renal function was assessed using glomerular filtration rate (GFR) based on age measure; Modification of Diet in Renal Disease (MDRD) formula for participants aged 18 years or older, defined as GFR equal to 32788*(serum creatinine (micromol/L)^-1.154)*(age^-0.203 )*(0.742, if female)*(1.210, if black), and Schwartz formula for participants less than 18 years defined as GFR equal to 0.41*height (cm)/ Serum creatinine (mg/dL). Participants with severe renal impairment defined as GFR < 30 mL/min/1.73 m^2 and participants with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 3/4 serum creatinine were reported.
Full Information
NCT ID
NCT00789828
First Posted
November 12, 2008
Last Updated
January 4, 2016
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00789828
Brief 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)
Acronym
EXIST-1
Official 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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma
Keywords
SEGA, Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma, mTOR, RAD001, Mamalian Target Rapamycin, Everolimus, TSC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
117 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo administered orally.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Everolimus was formulated as tablets of 1.0-mg strength and was blisterpacked under aluminum foil in units of 10 tablets.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo was provided as a matching tablet and was blisterpacked under aluminum foil in units of 10.
Primary Outcome Measure Information:
Title
Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response
Description
Participants were assessed for SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilized to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.
Time Frame
End of core period (Week 48), and end of extension period (up to 4 years)
Secondary Outcome Measure Information:
Title
Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period
Description
Seizure frequency per 24 hours was defined as the number of seizures in the electroencephalography (EEG) divided by the number of hours in the EEG, multiplied by 24. Seizure frequency was evaluated using a 24-hour video-EEG. Seizure frequency was listed as missing if the actual EEG recording duration was < 18 hours.
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)
Title
Time to SEGA Progression
Description
Time to SEGA progression was defined as time between randomisation to time to first SEGA progression. SEGA progression was defined as either one or more of the following criteria: 1. increase from nadir of ≥ 25% in SEGA volume to a value greater than baseline SEGA volume (where SEGA volume is the sum of the volumes of all target SEGA lesions identified at baseline, and nadir is the lowest SEGA volume obtained for the participant previously in the trial), 2. unequivocal worsening of non-target SEGA lesions, 3. appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, 4. new or worsening hydrocephalus. The median TTSP based on central radiology review was not reached in any treatment arms; Only 6 events of SEGA progressions were observed in the placebo group of core period.
Time Frame
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Title
Time to SEGA Response
Description
Participants were assessed for time to SEGA response, defined as 50% reduction from baseline in SEGA volume (where SEGA volume was the sum of the volumes of all target SEGA lesions identified at baseline, and confirmed with a second scan performed approximately 12 weeks later), no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus. Multi-phase brain MRI was utilised to identify SEGA lesions. SEGA response rate was defined as the percentage of participants whose best overall status was SEGA response as determined by Independent Central Radiology Review. The Kaplan-Meier estimate was used for determining time to SEGA response.
Time Frame
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Title
Duration of SEGA Response
Description
Duration of SEGA response was defined as time from the date of the first documented SEGA response until the date of the first documented SEGA progression. Duration of SEGA response was evaluated only for participants who achieved a SEGA response. The time to SEGA progression was censored if SEGA progression was not observed before the first to occur out of (i) analysis cut-off date (ii) the date when systemic anti-SEGA medication is started, (iii) the date of a SEGA-related surgery or (iv) the date of death. Since, no case of SEGA progression was observed in core study which resulted in censored duration of SEGA response. Only 5 SEGA responders experienced a SEGA progression in extension period.
Time Frame
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Title
Time to SEGA Worsening
Description
Time to SEGA worsening was defined as the time from the start of everolimus to date of the first SEGA worsening. SEGA worsening was defined as either; increase from nadir of ≥ 25% in SEGA volume or unequivocal worsening of non-target SEGA lesions, or appearance of new SEGA lesion ≥ 1.0 cm in longest diameter, or new or worsening hydrocephalus. The median value was not reached in either treatment arm of core period as SEGA worsening was observed in less participants (everolimus - 7 and placebo - 8).
Time Frame
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Title
Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score
Description
Skin lesions included hypomelanotic macules, the shagreen patch, periungual or subungual fibromas, facial angiofibromas and/or forehead plaques. Response was evaluated using the Physician's Global Assessment of Clinical Condition (PGA) on a 7-point scale: Grade 0 = complete clinical response, indicated absence of disease, Grade 1, 2, and 3 = partial response, indicated improvements of ≥ 50% but < 100%, Grade 4, 5 = stable disease, indicated some or no improvements of 25% - < 50% and 6 = progressive disease, indicated worse than at baseline evaluation by > 25%. Response rate was determined for participants with ≥ 1 skin lesion at baseline, defined as the percentage of participants with overall status as complete clinical response or partial response.
Time Frame
End of core period (Week 48), and end of extension period (up to 4 years)
Title
Duration of Skin Lesion Response in Everolimus Treated Participants
Description
Duration of skin lesion response was defined as the time from the first skin lesion response until the first skin lesion progression, defined as worsening of lesion by > 25% or more from baseline.
Time Frame
Baseline up to week 48 (end of core period), and end of extension period (up to 4 years)
Title
Everolimus Blood Concentration (C2h) at 2 Hours Post Dose
Description
The participants were assessed for everolimus blood concentration at 2 hours time point after dose administration on the same day, if the participant did not vomit between previous dose and blood sample collection. Tandem liquid chromatography-mass spectrometry method was used for evaluation. C2h values were categorized as < 20 ng/mL, 20-50 ng/mL, and > 50 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.
Time Frame
2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240
Title
Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose
Description
The participants were assessed for everolimus trough concentration (Cmin) at 24 hours time point after previous dose administration, at a steady state following 5 days of consistent dosing, if the participant did not vomit within 4 hours of previous dose. Tandem liquid chromatography-mass spectrometry method was used for evaluation. Cmin values were categorized as <5 ng/mL, 5-10 ng/mL, and >10 ng/mL, concentrations below the lower limit of quantification were entered as 0 ng/mL.
Time Frame
24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240
Title
Percentage of Participants With Renal Impairment During Core Period
Description
Renal function was assessed using glomerular filtration rate (GFR) based on age measure; Modification of Diet in Renal Disease (MDRD) formula for participants aged 18 years or older, defined as GFR equal to 32788*(serum creatinine (micromol/L)^-1.154)*(age^-0.203 )*(0.742, if female)*(1.210, if black), and Schwartz formula for participants less than 18 years defined as GFR equal to 0.41*height (cm)/ Serum creatinine (mg/dL). Participants with severe renal impairment defined as GFR < 30 mL/min/1.73 m^2 and participants with National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 3/4 serum creatinine were reported.
Time Frame
Day 1 up to 28 days after end of treatment (Core period)
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticlas
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Barrow Tuberous Sclerosis Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Children's Hospital Oakland Hematology/Oncology Dept
City
Oakland
State/Province
California
ZIP/Postal Code
94609-1809
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
University of CHicago Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Massachusetts General Hospital Mass General
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Children's Hospital Boston SC-1
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Minnesota Epilepsy Group - PA
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55102-2383
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center Cincinnati Children's Hosp
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Texas Scottish Rite Hospital for Children
City
Dallas
State/Province
Texas
ZIP/Postal Code
75219
Country
United States
Facility Name
Children's Regional Outpatients Center SC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Novartis Investigative Site
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2130
Country
Australia
Facility Name
Novartis Investigative Site
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
H3T IC5
Country
Canada
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16147
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
ZIP/Postal Code
00137
Country
Italy
Facility Name
Novartis Investigative Site
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
127412
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Bristol
ZIP/Postal Code
BS1 3NU
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
30053159
Citation
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.
Results Reference
derived
PubMed Identifier
29023494
Citation
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.
Results Reference
derived
PubMed Identifier
27351628
Citation
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.
Results Reference
derived
PubMed Identifier
26858193
Citation
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.
Results Reference
derived
PubMed Identifier
25682485
Citation
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.
Results Reference
derived
PubMed Identifier
25456370
Citation
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.
Results Reference
derived
PubMed Identifier
24729041
Citation
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.
Results Reference
derived
PubMed Identifier
23733802
Citation
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.
Results Reference
derived
PubMed Identifier
23158522
Citation
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. Erratum In: Lancet. 2013 Jan 12;381(9861):116.
Results Reference
derived
Links:
URL
http://www.novartisclinicaltrials.com/webapp/portals/EXISTClinicalTrials/page.do
Description
Visit EXIST-1 NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.
Learn more about this trial
Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
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