Back to resultsEverolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex
Primary Purpose
Tuberous Sclerosis, Subependymal Giant Cell Astrocytoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Tuberous Sclerosis focused on measuring Tuberous Sclerosis Complex (TSC), Subendymal Giant Cell Astrocytomas (SEGA'S), Mammalian Target of Rapamycin (mTOR), Everolimus (RAD001), Tuberous Sclerosis with Subependymal Giant Cell Astrocytomas
Eligibility Criteria
Inclusion Criteria:
- Age three years and older
- If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. In the extension phase, all females of child bearing potential will be required to take monthly home pregnancy tests and record results on a provided diary card.
- Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria or positive genetic test)
- Presence of giant cell astrocytoma as defined by imaging characteristics and serial increase in size of lesion on 2 or more MRI scans
- Adequate renal function (creatinine < 1.5 mg/dl)
Exclusion Criteria:
- Serious intercurrent medical illness or other uncontrolled medical disease which could compromise participation in the study
- Significant hematologic or hepatic abnormality
- Continuous requirement for supplemental oxygen
- Intercurrent infection at initiation of everolimus
- Embolization of angiomyolipoma within one month; any other recent surgery within 2 months of initiation of everolimus
- Pregnant or lactating women
- Use of an investigational drug within the last 30 days
- Must be adequately recovered from the acute toxicities of any prior therapy
- Clinical evidence of impending herniation or focal neurologic deficit related to the subject's astrocytoma
- Unwilling or unable to use highly effective contraception
Sites / Locations
- Cincinnati Children's Hospital Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Everolimus
Arm Description
As this was a non-randomized, open-label, single arm study, all patients in the study received treatment with everolilmus
Outcomes
Primary Outcome Measures
Number With Observed Adverse Side Effects
Secondary Outcome Measures
Overall Reduction in SEGA Tumor Volume.
Full Information
NCT ID
NCT00411619
First Posted
December 12, 2006
Last Updated
October 17, 2014
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT00411619
Brief Title
Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex
Official Title
Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to evaluate the safety and potential side effects of everolimus (an experimental drug) on a person with Tuberous Sclerosis Complex who also has been diagnosed with a brain tumor (astrocytoma)
The hypothesis is that the drug will cause the tumor size to decrease, and may have beneficial activity separate from effects on tumors in patients.
Detailed Description
Tuberous Sclerosis Complex (TSC)is a genetic disorder with a birth incidence of approximately one in six thousand. Five to twenty percent of patients with TSC will develop astrocytoma, a slowly progressive tumor. They grow and cause damage to surrounding brain tissue, blockage of spinal fluid (hydrocephalus), blindness, trouble walking, seizures, and brain damage. If untreated, they can be fatal. Standard treatment involves surgery to remove the tumor; however surgery may itself cause brain damage, bleeding, or infection, as well as other complications. Studies have shown that everolimus suppresses the chemicals that cause tumors to grow in tuberous sclerosis, and may cause them to shrink.
The primary objective of this study is to find out the effects of everolimus on astrocytomas in a six month trial in patients with Tuberous Sclerosis who have been diagnosed with an astrocytoma
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
Tuberous Sclerosis Complex (TSC), Subendymal Giant Cell Astrocytomas (SEGA'S), Mammalian Target of Rapamycin (mTOR), Everolimus (RAD001), Tuberous Sclerosis with Subependymal Giant Cell Astrocytomas
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
As this was a non-randomized, open-label, single arm study, all patients in the study received treatment with everolilmus
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Initial everolimus dosage will be 3 mg/m2/d taken daily or every other day, with titration to achieve a trough serum level of 5-15 ng/ml. Patients unable to tolerate levels in this range will have doses held or reduced 25% to achieve trough serum levels of 5-10 ng/ml. If trough serum level of 5-15 ng/ml is not achieved at a dosage of 3 mg/m2/d, then dosage escalation by 25% will be undertaken as tolerated. Everolimus will be similarly adjusted during the extension phase. If a subject misses more than 10 consecutive everolimus doses, additional days of everolimus treatment will be added so total duration of treatment is 6 months. If this occurs, dates of subsequent study events will be adjusted according to number of missed doses. This process will also be followed in the extension phase.
Primary Outcome Measure Information:
Title
Number With Observed Adverse Side Effects
Time Frame
During the entire study
Secondary Outcome Measure Information:
Title
Overall Reduction in SEGA Tumor Volume.
Time Frame
During the entire study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age three years and older
If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. In the extension phase, all females of child bearing potential will be required to take monthly home pregnancy tests and record results on a provided diary card.
Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria or positive genetic test)
Presence of giant cell astrocytoma as defined by imaging characteristics and serial increase in size of lesion on 2 or more MRI scans
Adequate renal function (creatinine < 1.5 mg/dl)
Exclusion Criteria:
Serious intercurrent medical illness or other uncontrolled medical disease which could compromise participation in the study
Significant hematologic or hepatic abnormality
Continuous requirement for supplemental oxygen
Intercurrent infection at initiation of everolimus
Embolization of angiomyolipoma within one month; any other recent surgery within 2 months of initiation of everolimus
Pregnant or lactating women
Use of an investigational drug within the last 30 days
Must be adequately recovered from the acute toxicities of any prior therapy
Clinical evidence of impending herniation or focal neurologic deficit related to the subject's astrocytoma
Unwilling or unable to use highly effective contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David N Franz, M.D.
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30424962
Citation
Peters JM, Prohl A, Kapur K, Nath A, Scherrer B, Clancy S, Prabhu SP, Sahin M, Franz DN, Warfield SK, Krueger DA. Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex. Pediatr Neurol. 2019 Jan;90:24-30. doi: 10.1016/j.pediatrneurol.2018.10.005. Epub 2018 Oct 18.
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
26381530
Citation
Franz DN, Agricola K, Mays M, Tudor C, Care MM, Holland-Bouley K, Berkowitz N, Miao S, Peyrard S, Krueger DA. Everolimus for subependymal giant cell astrocytoma: 5-year final analysis. Ann Neurol. 2015 Dec;78(6):929-38. doi: 10.1002/ana.24523. Epub 2015 Nov 9.
Results Reference
derived
PubMed Identifier
23325902
Citation
Krueger DA, Care MM, Agricola K, Tudor C, Mays M, Franz DN. Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma. Neurology. 2013 Feb 5;80(6):574-80. doi: 10.1212/WNL.0b013e3182815428. Epub 2013 Jan 16.
Results Reference
derived
PubMed Identifier
22262746
Citation
Tillema JM, Leach JL, Krueger DA, Franz DN. Everolimus alters white matter diffusion in tuberous sclerosis complex. Neurology. 2012 Feb 21;78(8):526-31. doi: 10.1212/WNL.0b013e318247ca8d. Epub 2012 Jan 18.
Results Reference
derived
PubMed Identifier
21047224
Citation
Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4;363(19):1801-11. doi: 10.1056/NEJMoa1001671.
Results Reference
derived
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Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex
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