Please select the eligibility criteria that correspond to the clinical trial below.
Title: Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex
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.


Options:
A: 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
B: Inclusion Criteria:

* Subjects must be willing and able to comply with all trial requirements.
* Subject has a diagnosis of TSC and has visible facial angiofibromas.
* Female subjects of child bearing potential must not be pregnant and must agree to use appropriate contraceptive methods .

Exclusion Criteria:

* Subject is currently receiving therapy with Rapamycin.
* Subject is receiving any form of immunosuppression or has previously experienced immune dysfunction.
* Subject is currently participating in or has participated within the last 30 days in a clinical trial involving an investigational drug.
* Subject has a known hypersensitivity to either the vehicle or Rapamycin.
* Subject is a pregnant or nursing female.
* Subject has other dermatologic conditions that would preclude or prevent adequate assessment of changes to their facial angiofibromas.
* Subject has had laser surgery, cryotherapy, or other dermatologic treatment to their facial angiofibromas within the previous 6 months.
C: Inclusion Criteria:

* Male or Female 18 years or older
* Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
* Clinically definite diagnosis of renal angiomyolipoma
* At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
* Females of child bearing potential must use birth control and have documentation of negative pregnancy test
* Written informed consent according to local guidelines

Exclusion Criteria:

* Recent heart attack, cardiac related chest pain or stroke
* Severely impaired lung function
* Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
* Clinically significant chylous ascites
* Clinically significant hematological or hepatic abnormality
* Severe liver dysfunction
* Severe kidney dysfunction
* Pregnancy or breast feeding
* Current infection
* History of organ transplant
* Surgery within two months prior to study enrollment
* Prior therapy with a medication in the same class as Everolimus
* Recent use of an investigational drug
* Bleeding diathesis or on oral anti-vitamin K medication
* Uncontrolled high cholesterol
* Uncontrolled diabetes
* HIV
* Inability to attend scheduled clinic visits
* Patients with metal implants thus prohibiting MRI evaluations
* Angiomyolipoma which requires surgery at the time of randomization
* History of malignancy
* Severe or uncontrolled medical conditions which would cause an unacceptable safety risk or compromise compliance with the protocol
D: Inclusion Criteria:

* If female, documentation of negative pregnancy test prior to enrolment.
* Participants, including males, must use an effective form of contraception, whilst taking sirolimus and for twelve weeks after stopping the drug
* One or more renal angiomyolipomata of at least two centimetres or greater in largest diameter
* Adequate renal function :glomerular filtration rate \> 40 ml/min
* Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria) or sporadic LAM (biopsy-proven or compatible high resolution chest CT scan and respiratory function tests.)
* Signed and dated informed consent

Exclusion Criteria:

* History of non-compliance or inability to give informed consent
* Significant haematological or hepatic abnormality (i.e. transaminase levels \> 150 i.u./L serum albumin \< 30 g/L, haematocrit\< 30%, platelets \< 100,000/ mm3, adjusted absolute neutrophil count \< 1,500/mm3, total WBC \< 3,000/ mm3)
* Greater than 1 g proteinuria daily
* Multiple bilateral AMLs, where individual lesions cannot be distinguished
* Renal haemorrhage within preceding year
* In those who have had a renal haemorrhage, known conservatively managed renal aneurysm(s) greater than 10mm
* Patients who have had embolisation for AML(s) within the preceding 6 months
* Patients who are unable to walk 100 metres on the flat
* Continuous requirement for supplemental oxygen
* Patients who have had or are being considered for organ transplant
* Uncontrolled hyperlipidaemia
* Intercurrent infection at initiation of Sirolimus
* Surgery within last 2 months
* Pregnant or lactating women
* Use of an investigational drug within the last 30 days
* Change in anti epileptic drug medication within the last 3 months
* Likely to need vaccination e.g. for travel during the course of the trial (except for influenza vaccine in patients with LAM)
* Current usage of strong inhibitors of CYP3AE ( such as ketoconazole, voriconazole, itraconazole, tilithromycin or clarithromycin) or strong inducers (such as rifampicin or rifabutin)

Answer: A