Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1)
This study is ongoing, but not recruiting participants.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00789828
First received: November 12, 2008
Last updated: March 25, 2013
Last verified: March 2013
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Results First Received: March 1, 2012
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, 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 |
|---|
| No text entered. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
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| Patients in the study were randomized in a 2:1 ratio (Everolimus: Placebo). |
Reporting Groups
| Description | |
|---|---|
| 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 | Matching Placebo was administered orally. |
Participant Flow: Overall Study
| Everolimus | Placebo | |
|---|---|---|
| STARTED | 78 | 39 |
| COMPLETED | 2 [1] | 8 |
| NOT COMPLETED | 76 | 31 |
| Ongoing in Double Blind | 76 | 31 |
| [1] | Completed means discontinued the double-blind treatment period. |
|---|
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| 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 | Matching Placebo was administered orally. |
| Total | Total of all reporting groups |
Baseline Measures
| Everolimus | Placebo | Total | |
|---|---|---|---|
|
Number of Participants
[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: | Subependymal Giant Cell Astrocytomas (SEGA) Response Rate [ Time Frame: From date of randomization until the earliest date of first documented SEGA progression, date of further anti-SEGA medication (including open-label Everolimus)/surgery or analysis cut-off date (02-Mar-2011) ] |
| 2. Secondary: | Change From Baseline to Week 24 in Total Seizure Frequency Per 24 Hours From Video EEG as Per Central Reader. [ Time Frame: Baseline, Week 24 ] |
| 3. Secondary: | Time to SEGA Progression Based on Independent Central Radiology Review [ Time Frame: From date of randomization until the earliest date of first documented SEGA progression, date of further anti-SEGA medication (including open-label Everolimus)/surgery or analysis cut-off date (02-Mar-2011) ] |
| 4. Secondary: | Skin Lesion Response Rate as Per Investigator Assessment Using the Physician's Global Assessment of Clinical Condition (PGA) [ Time Frame: From date of randomization until the earliest date of first skin lesion progression, date of start of further therapy against skin lesions (including open-label Everolimus) or analysis cut-off date (02-Mar-2011) ] |
| 5. Secondary: | Change From Baseline in Angiogenesis Biomarkers [ Time Frame: Baseline, Week 4, Week 12, Week 24, Week 36 and Week 48 ] |
Results not yet posted. Anticipated Posting Date:
09/2014
Safety Issue:
No
| 6. Secondary: | Changes in Renal Function Assessed Using Creatinine Clearance/Globerular Filtration Rate. [ Time Frame: From start of treatment and assessed on a continuous basis through the duration of the study ] |
Results not yet posted. Anticipated Posting Date:
09/2014
Safety Issue:
Yes
Serious Adverse Events| Time Frame | No text entered. |
|---|---|
| Additional Description | No text entered. |
Reporting Groups
| Description | |
|---|---|
| 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 | Matching placebo was administered orally. |
Serious Adverse Events
| Everolimus | Placebo | |
|---|---|---|
| Total, serious adverse events | ||
| # participants affected / at risk | 15/78 (19.23%) | 3/39 (7.69%) |
| Gastrointestinal disorders | ||
| Abdominal pain † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| General disorders | ||
| Pyrexia † 1 | ||
| # participants affected / at risk | 3/78 (3.85%) | 0/39 (0.00%) |
| Immune system disorders | ||
| Hypersensitivity † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Infections and infestations | ||
| Adenovirus infection † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Bronchitis † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 1/39 (2.56%) |
| Bronchopneumonia † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Febrile infection † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Gastroenteritis † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 0/39 (0.00%) |
| Gastroenteritis viral † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 0/39 (0.00%) |
| Gastrointestinal infection † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Otitis media † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Pneumonia † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 0/39 (0.00%) |
| Respiratory tract infection viral † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Upper respiratory tract infection † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 0/39 (0.00%) |
| Urinary tract infection † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Metabolism and nutrition disorders | ||
| Dehydration † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Nervous system disorders | ||
| Convulsion † 1 | ||
| # participants affected / at risk | 3/78 (3.85%) | 2/39 (5.13%) |
| Grand mal convulsion † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| Status epilepticus † 1 | ||
| # participants affected / at risk | 2/78 (2.56%) | 0/39 (0.00%) |
| Psychiatric disorders | ||
| Agitation † 1 | ||
| # participants affected / at risk | 1/78 (1.28%) | 0/39 (0.00%) |
| † | Events were collected by systematic assessment |
|---|---|
| 1 | Term from vocabulary, MedDRA 13.1 |
Other Adverse Events