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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00411619
First received: December 12, 2006
Last updated: December 12, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Tuberous Sclerosis
Subependymal Giant Cell Astrocytoma
Drug: Everolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Primary Outcome Measure will be incidence of reported and observed adverse side effects as a percentage of patients enrolled in the study and treated with everolimus. These will be analysed at 6 months after study initiation. [ Time Frame: During the entire study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary Outcome Measures include overall reduction in SEGA tumor volume. [ Time Frame: MRIs at baseline, month 3 and end of study (month 6), ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: December 2006
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Everolimus
    The 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 their doses held or reduced 25% with the goal of achieving trough serum levels of 5-10 ng/ml. If a trough serum level of 5-15 ng/ml is not achieved at a dosage of 3 mg/m2/d, then further 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, the dates of the 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
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

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00411619

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Novartis
Investigators
Principal Investigator: David N Franz, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided by Children's Hospital Medical Center, Cincinnati

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00411619     History of Changes
Other Study ID Numbers: CCHMC IRB# 06-07-50
Study First Received: December 12, 2006
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

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:
Sclerosis
Tuberous Sclerosis
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Pathologic Processes
Hamartoma
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014