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Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00411619
Recruitment Status : Completed
First Posted : December 14, 2006
Results First Posted : October 20, 2014
Last Update Posted : October 20, 2014
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

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.

Condition or disease Intervention/treatment Phase
Tuberous Sclerosis Subependymal Giant Cell Astrocytoma Drug: Everolimus Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex
Study Start Date : January 2007
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Arm Intervention/treatment
Experimental: Everolimus
As this was a non-randomized, open-label, single arm study, all patients in the study received treatment with everolilmus
Drug: Everolimus
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.
Other Name: RAD001

Primary Outcome Measures :
  1. Number With Observed Adverse Side Effects [ Time Frame: During the entire study ]

Secondary Outcome Measures :
  1. Overall Reduction in SEGA Tumor Volume. [ Time Frame: During the entire study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00411619

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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
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Principal Investigator: David N Franz, M.D. Children's Hospital Medical Center, Cincinnati
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT00411619    
Other Study ID Numbers: CCHMC IRB# 06-07-50
First Posted: December 14, 2006    Key Record Dates
Results First Posted: October 20, 2014
Last Update Posted: October 20, 2014
Last Verified: October 2014
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Tuberous Sclerosis Complex (TSC)
Subendymal Giant Cell Astrocytomas (SEGA'S)
Mammalian Target of Rapamycin (mTOR)
Everolimus (RAD001)
Tuberous Sclerosis with Subependymal Giant Cell Astrocytomas
Additional relevant MeSH terms:
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Tuberous Sclerosis
Pathologic Processes
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs