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

Tuberous Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00411619
• Other study ID #: CCHMC IRB# 06-07-50
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 12, 2006
• Last updated: October 17, 2014
• Start date: January 2007
• Est. completion date: January 2014

Study information

• Verified date: October 2014
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Astrocytoma
• Sclerosis
• Subependymal Giant Cell Astrocytoma
• Tuberous Sclerosis

Intervention

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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number With Observed Adverse Side Effects		During the entire study	Yes
Secondary	Overall Reduction in SEGA Tumor Volume.		During the entire study	No