Trial · NCT00789828
Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
NCT00789828, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2012-05-01
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1). Trials, record NCT00789828. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT00789828
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- 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)
- NCT number
- NCT00789828
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 117 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma
- Interventions
- Everolimus, Placebo
- First posted
- 2008-11-13
- Last updated
- 2016-02-03
- Other registries' IDs
- eudract:2007-006997-27
- Results first posted
- 2012-05-01
Source ClinicalTrials.gov
Registered outcomes11
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response | End of core period (Week 48), and end of extension period (up to 4 years) | 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 | Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period | 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) | 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. |
| Secondary | Time to SEGA Progression | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | 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. |
| Secondary | Time to SEGA Response | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | 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. |
| Secondary | Duration of SEGA Response | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | 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. |
| Secondary | Time to SEGA Worsening | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | 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). |
| Secondary | Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score | End of core period (Week 48), and end of extension period (up to 4 years) | 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. |
| Secondary | Duration of Skin Lesion Response in Everolimus Treated Participants | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | 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. |
| Secondary | Everolimus Blood Concentration (C2h) at 2 Hours Post Dose | 2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240 | 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. |
| Secondary | Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose | 24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240 | 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. |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 registered outcomesOutcomes11
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response | End of core period (Week 48), and end of extension period (up to 4 years) | The primary analysis was performed in Full Analysis Set (FAS) population, defined as all randomized participants involved in the study. | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period | 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) | The analysis was performed in the FAS population. Missing values were imputed using last observation carried forward approach for core period while raw count for extension period. | Seizure frequency | MEAN |
| SECONDARY | Time to SEGA Progression | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. Here Number of participants analysed signifies the participants assessed for time to SEGA progression during the study for each arm, respectively. | months | MEDIAN |
| SECONDARY | Time to SEGA Response | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. | months | MEDIAN |
| SECONDARY | Duration of SEGA Response | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. Here, Number of participants analysed signifies the participants assessed for SEGA progression during the study for each arm, respectively. | months | MEDIAN |
| SECONDARY | Time to SEGA Worsening | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. Here, Number of participants analysed signifies the participants assessed for time to SEGA worsening during the study for each arm, respectively. | months | MEDIAN |
| SECONDARY | Percentage of Participants With Skin Lesions Assessed Using Physician's Global Assessement Overall Score | End of core period (Week 48), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. Here, Number of participants analysed signifies the participants assessed for skin lesion response during the study for each arm, respectively. | Percentage of participants | NUMBER |
| SECONDARY | Duration of Skin Lesion Response in Everolimus Treated Participants | Baseline up to week 48 (end of core period), and end of extension period (up to 4 years) | The analysis was performed in the FAS population. Here, Number of participants analysed signifies everolimus treated responders with best overall skin lesion response during the core and extension period, respectively. | months | MEDIAN |
| SECONDARY | Everolimus Blood Concentration (C2h) at 2 Hours Post Dose | 2 hours post dose on Week 6, Week 24, Week 48, Week 96, Week 144, and Week 240 | The analysis was performed in the Safety Set population (Only evaluable PK Samples), defined as participants who received at least one dose of the double-blind study drug, with a valid post baseline assessment. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | ng/mL | MEAN |
| SECONDARY | Everolimus Trough Concentrations (Cmin) at 24 Hours After Last Dose | 24 hours post dose on Week 6, Week 24, Week 48, Week 72, Week 96, Week 144, and Week 240 | The analysis was performed in the Safety Set population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | ng/mL | MEAN |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 outcomesResults by group53
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response | Everolimus (Core Period) | 34.6 | 95% Confidence Interval 24.2 to 46.2 | Percentage of participants | |
| Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response | Placebo (Core Period) | 0.0 | 95% Confidence Interval 0.0 to 9.0 | Percentage of participants | |
| Percentage of Participants With Best Overall Subependymal Giant Cell Astrocytomas (SEGA) Response | Everolimus (Extension Period) | 57.7 | 95% Confidence Interval 47.9 to 67 | Percentage of participants | |
| Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period | Everolimus (Core Period) | -1.24 | Standard Deviation 6.12 | Seizure frequency | |
| Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period | Placebo (Core Period) | -0.24 | Standard Deviation 5.7 | Seizure frequency | |
| Change From Baseline in Frequency of Total Seizure Events Per 24 Hours at Week 24 in Both Core and Extension Period | Everolimus (Extension Period) | -6.07 | Standard Deviation 9.719 | Seizure frequency | |
| Time to SEGA Progression | Everolimus (Core Period) | NA | 95% Confidence Interval NA to NA | months | |
| Time to SEGA Progression | Placebo (Core Period) | NA | 95% Confidence Interval NA to NA | months | |
| Time to SEGA Progression | Everolimus (Extension Period) | NA | 95% Confidence Interval NA to NA | months | |
| Time to SEGA Response | Everolimus (Core Period) | 2.99 | 95% Confidence Interval 2.79 to 5.36 | months |
1 to 10 of 53Source ClinicalTrials.gov
See all 53 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Core Period (48 Weeks) | STARTED | Everolimus | 78 | |
| Core Period (48 Weeks) | STARTED | Placebo | 39 | |
| Core Period (48 Weeks) | COMPLETED | Everolimus | 78 | |
| Core Period (48 Weeks) | COMPLETED | Placebo | 33 | |
| Core Period (48 Weeks) | NOT COMPLETED | Everolimus | 0 | |
| Core Period (48 Weeks) | NOT COMPLETED | Placebo | 6 | |
| Open-label Extension Period (4 Years) | STARTED | Everolimus | 111 | |
| Open-label Extension Period (4 Years) | STARTED | Placebo | 0 | |
| Open-label Extension Period (4 Years) | COMPLETED | Everolimus | 82 | |
| Open-label Extension Period (4 Years) | COMPLETED | Placebo | 0 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events513
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Everolimus Treated (Core and Extension Period) | 6 | 78 | |
| other | Anaemia | Blood and lymphatic system disorders | Placebo (Core) Then Everolimus Treated (Extension Period) | 1 | 33 | |
| other | Anaemia | Blood and lymphatic system disorders | Placebo Treated (Core Period) | 0 | 6 | |
| other | Neutropenia | Blood and lymphatic system disorders | Everolimus Treated (Core and Extension Period) | 8 | 78 | |
| other | Neutropenia | Blood and lymphatic system disorders | Placebo (Core) Then Everolimus Treated (Extension Period) | 3 | 33 | |
| other | Neutropenia | Blood and lymphatic system disorders | Placebo Treated (Core Period) | 0 | 6 | |
| other | Ear pain | Ear and labyrinth disorders | Everolimus Treated (Core and Extension Period) | 2 | 78 | |
| other | Ear pain | Ear and labyrinth disorders | Placebo (Core) Then Everolimus Treated (Extension Period) | 2 | 33 | |
| other | Ear pain | Ear and labyrinth disorders | Placebo Treated (Core Period) | 0 | 6 | |
| other | Vertigo | Ear and labyrinth disorders | Everolimus Treated (Core and Extension Period) | 0 | 78 |
1 to 10 of 513Source ClinicalTrials.gov
See all 513 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Everolimus Treated (Core and Extension Period) | ||
| Total, all-cause mortality | Placebo (Core) Then Everolimus Treated (Extension Period) | ||
| Total, all-cause mortality | Placebo Treated (Core Period) | ||
| Total, other adverse events | Everolimus Treated (Core and Extension Period) | 77 | 78 |
| Total, other adverse events | Placebo (Core) Then Everolimus Treated (Extension Period) | 33 | 33 |
| Total, other adverse events | Placebo Treated (Core Period) | 6 | 6 |
| Total, serious adverse events | Everolimus Treated (Core and Extension Period) | 33 | 78 |
| Total, serious adverse events | Placebo (Core) Then Everolimus Treated (Extension Period) | 17 | 33 |
| Total, serious adverse events | Placebo Treated (Core Period) | 3 | 6 |
Source ClinicalTrials.gov
Papers9
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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