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 has been completed.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00789828
First received: November 12, 2008
Last updated: October 31, 2014
Last verified: October 2014
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Purpose
This study evaluated the efficacy and safety of Everolimus in treating patients with Subependymal Giant Cell Astrocytomas associated with Tuberous Sclerosis Complex.
| Condition | Intervention | Phase |
|---|---|---|
|
Tuberous Sclerosis Subependymal Giant Cell Astrocytoma |
Drug: Everolimus Drug: Placebo |
Phase 3 |
| 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 |
| 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) |
Resource links provided by NLM:
Genetics Home Reference related topics:
tuberous sclerosis complex
MedlinePlus related topics:
Tuberous Sclerosis
Genetic and Rare Diseases Information Center resources:
Anaplastic Astrocytoma
Bourneville Syndrome
Glioma
Gliosarcoma
Neuroepithelioma
Subependymal Giant Cell Astrocytoma
Tuberous Sclerosis
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- 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) ] [ Designated as safety issue: No ]Sega response Rate is defined as the percentage of patients whose best overall status is response as determined by Independent Central Radiology Review. SEGA response was defined as: (1) a ≥ 50% reduction in SEGA volume relative to baseline (where SEGA volume was the sum of all target SEGA lesion volumes identified at baseline); and (2) no unequivocal worsening of non-target SEGA lesions, no new SEGA lesions (≥ 1 cm in longest diameter), and no new or worsening hydrocephalus.
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]The video EEG recordings were sent to a Central Reader for interpretation and recording of seizure frequency/type. Seizure frequency per 24 hours is defined as the number of seizures in the EEG divided by the number of hours in the EEG, multiplied by 24. Seizure frequency was listed as missing if the actual EEG recording duration was <18 hours.
- 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) ] [ Designated as safety issue: No ]Time to SEGA progression was defined as time from date of randomization to date of first documented SEGA progression. SEGA progression was defined as one or more of: 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 where nadir is the lowest SEGA volume obtained for the patient previously in the trial) 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
- 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) ] [ Designated as safety issue: No ]Response rate determined among patients with ≥ 1 skin lesion at baseline (BL) and defined as the percentage of patients whose best overall status is complete clinical response or partial response. Response was evaluated using the PGA which is a 7-point scale that allows the investigator to evaluate improvement or worsening of the patient's skin disease compared to BL. Assessment was designed to consider skin lesions as a whole. Complete clinical response required a grading of 0 indicating the absence of disease. Grade 1, 2, and 3 = partial response, indicating improvements of ≥ 50% but < 100%
- Change From Baseline in Angiogenesis Biomarkers [ Time Frame: Baseline, Week 4, Week 12, Week 24, Week 36 and Week 48 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
| Enrollment: | 118 |
| Study Start Date: | August 2009 |
| Study Completion Date: | October 2014 |
| Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
Drug: Everolimus
Everolimus was formulated as tablets of 1.0-mg strength and was blisterpacked under aluminum foil in units of 10 tablets.
Other Name: RAD001
|
|
Placebo Comparator: Placebo
Matching Placebo administered orally.
|
Drug: Placebo
Placebo was provided as a matching tablet and was blisterpacked under aluminum foil in units of 10.
|
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00789828
Show 24 Study Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00789828
Show 24 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticlas | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00789828 History of Changes |
| Other Study ID Numbers: | CRAD001M2301, 2007-006997-27 |
| Study First Received: | November 12, 2008 |
| Results First Received: | March 1, 2012 |
| Last Updated: | October 31, 2014 |
| Health Authority: | United States: Food and Drug Administration Belgium: Federal Agency for Medicines and Health Products, FAMHP Germany: Federal Institute for Drugs and Medical Devices Italy: Ministry of Health Netherlands: Medicines Evaluation Board (MEB) Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products United Kingdom: Medicines and Healthcare Products Regulatory Agency Australia: Department of Health and Ageing Therapeutic Goods Administration |
Keywords provided by Novartis:
|
SEGA Tuberous Sclerosis Subependymal Giant Cell Astrocytoma mTOR |
RAD001 Mamalian Target Rapamycin Everolimus TSC |
Additional relevant MeSH terms:
|
Sclerosis Tuberous Sclerosis Astrocytoma Gliosarcoma Congenital Abnormalities Genetic Diseases, Inborn Glioma Hamartoma Heredodegenerative Disorders, Nervous System Malformations of Cortical Development Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Multiple Primary |
Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplastic Syndromes, Hereditary Nervous System Diseases Nervous System Malformations Neurocutaneous Syndromes Neurodegenerative Diseases Neuroectodermal Tumors Pathologic Processes Everolimus Sirolimus Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents |
ClinicalTrials.gov processed this record on March 03, 2015