Subependymal Giant Cell Astrocytoma, Tuberous Sclerosis
Conditions
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
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
Interventions
DRUGEverolimus
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.
Sponsors
Novartis
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number With Observed Adverse Side Effects | During the entire study |
Secondary
| Measure | Time frame |
|---|---|
| Overall Reduction in SEGA Tumor Volume. | During the entire study |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Everolimus This was a non-randomized, open-label, single arm study; all patients in the study received treatment with everolimus. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Everolimus |
|---|---|
| Age, Categorical <=18 years | 22 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 9 / 28 |
Outcome results
Primary
Number With Observed Adverse Side Effects
Time frame: During the entire study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus | Number With Observed Adverse Side Effects | Laceration | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Nasal Congestion | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Dermatitis Acneiform | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Dermatitis Contact | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Upper Respiratory Tract Infection | 26 participants |
| Everolimus | Number With Observed Adverse Side Effects | Stomatitis | 25 participants |
| Everolimus | Number With Observed Adverse Side Effects | Sinusitis | 15 participants |
| Everolimus | Number With Observed Adverse Side Effects | Mouth Ulceration | 14 participants |
| Everolimus | Number With Observed Adverse Side Effects | Cellulitis | 12 participants |
| Everolimus | Number With Observed Adverse Side Effects | Diarrhoea | 12 participants |
| Everolimus | Number With Observed Adverse Side Effects | Gastroenteritis | 12 participants |
| Everolimus | Number With Observed Adverse Side Effects | Excoriation | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Otitis Media | 11 participants |
| Everolimus | Number With Observed Adverse Side Effects | Pyrexia | 10 participants |
| Everolimus | Number With Observed Adverse Side Effects | Vomiting | 10 participants |
| Everolimus | Number With Observed Adverse Side Effects | Acne | 9 participants |
| Everolimus | Number With Observed Adverse Side Effects | Convulsion | 9 participants |
| Everolimus | Number With Observed Adverse Side Effects | Nasopharyngitis | 9 participants |
| Everolimus | Number With Observed Adverse Side Effects | Rhinitis Allergic | 9 participants |
| Everolimus | Number With Observed Adverse Side Effects | Conjunctivitis | 8 participants |
| Everolimus | Number With Observed Adverse Side Effects | Pharyngitis | 8 participants |
| Everolimus | Number With Observed Adverse Side Effects | Rash | 8 participants |
| Everolimus | Number With Observed Adverse Side Effects | Constipation | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Cough | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Otitis Externa | 7 participants |
| Everolimus | Number With Observed Adverse Side Effects | Abnormal Behaviour | 6 participants |
| Everolimus | Number With Observed Adverse Side Effects | Body Tinea | 6 participants |
| Everolimus | Number With Observed Adverse Side Effects | Dry Skin | 6 participants |
| Everolimus | Number With Observed Adverse Side Effects | Pneumonia | 6 participants |
| Everolimus | Number With Observed Adverse Side Effects | Skin Infection | 6 participants |
| Everolimus | Number With Observed Adverse Side Effects | Urinary Tract Infection | 6 participants |
Secondary
Overall Reduction in SEGA Tumor Volume.
Time frame: During the entire study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus | Overall Reduction in SEGA Tumor Volume. | # with reductions > 30% relative to baseline | 14 participants |
| Everolimus | Overall Reduction in SEGA Tumor Volume. | # with reductions > 50% relative to baseline | 12 participants |