Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Multi-Center Study of Rapamycin for Treating Kidney Angiomyolipomas in TSC or LAM Patients
Brief Summary: This research study is evaluating a drug called rapamycin as a possible treatment for the lumps (or tumors) that form in the kidneys, called angiomyolipomas, in people who have either TSC or LAM. Kidney angiomyolipomas are tumors that are made up of blood vessels, muscle and fat. Rapamycin has been approved to treat other diseases, but it is investigational for treating kidney angiomyolipomas.

Investigational means that it is being as a possible treatment for kidney angiomyolipomas but is not currently approved by the U.S. Food and Drug Administration (FDA) for treating this disease.


Options:
A: 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
B: Inclusion Criteria:

* Age 3-65 years old (females of reproductive age must not be pregnant or breastfeeding)
* Kidney ANGIOMYOLIPOMA 2 cm or greater on baseline MRI (a CT scan may be used for patients who cannot undergo MRI imaging)
* No evidence of severe LAM (not on continuous oxygen)
* Informed consent, including consent for submission of blood, urine and tissue samples as described in the appendix.
* Adequate renal and liver function (eGFR of 30 or higher, SGOT, SGPT, TBili, Alk Phos all\<2x normal)
* HCT\>27%
* ANC \> 1500 and platelet count \>100,000
* Diagnosis of TSC or LAM (diagnosis of TSC using revised diagnostic criteria \[45\], diagnosis of LAM made by chest CT scan and reviewed by a pulmonologist).
* Fertility/Reproductive issues: The effects of rapamycin on the developing fetus at the doses used in this study are unknown. For this reason, rapamycin should not be taken during pregnancy. Participants who are fertile must maintain adequate contraception while they are taking rapamycin and for twelve weeks after stopping the drug. Acceptable contraceptive measures include prior hysterectomy, oophorectomy or tubal ligation, complete abstinence, barrier methods which include both a cervical diaphragm and spermicidal jelly, and progestin based contraceptives. Pregnancy tests will be obtained at enrollment and during study visits at 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, and 52 weeks.

  * Note: Eligibility requirement of ECOG PS of 0 or 1 has been removed to allow participation of those subjects with TSC who are classified as ECOG PS of 2,3, or 4 because of cognitive impairment rather than progressive disease. This change allows site Pl's to individualize decision making on whether or not to enroll such subjects after discussing details of the study with prospective participant and legal guardian. The decision to enroll individuals with ECOG PS of 2,3, or 4 will be at the discretion of the Principal Investigator.

Exclusion criteria:

* Unstable seizures (defined as changes in anti-epileptics OR increase in frequency and/or severity or seizures in the 60 days prior to study entry)
* Significant bleed associated with kidney angiomyolipoma(s) (defined as bleed associated with shock OR requiring a blood transfusion in the 30 days prior to study entry)
* Severe LAM (defined as dependent on continuous supplemental oxygen)
* Evidence for accelerating renal dysfunction or acute renal failure
* Diagnosis of Renal Cell Cancer that has not been treated (additional clarification: individuals with a prior history of renal cancer who have had appropriate surgery and have no evidence of metastatic disease can be enrolled)
* Active infection
* Patients will be excluded if they have been treated with any investigational agent in the 30 days prior to study entry
* Patients may not be treated with other investigational agents while on study
* Prior history of coronary artery disease
* Vascular embolization for treatment of kidney angiomyolipoma(s) within 6 months
* Patients who must take diltiazem, ketoconazole or rifampin chronically will be excluded because of known drug interactions. Both diltiazem and ketoconazole are strong inhibitors of CYP3A4 and are known to increase rapamycin levels. Rifampin is a known CYP3A4 and P-glycoprotein inducer and is known to significantly reduce rapamycin levels.
C: Inclusion Criteria:

* Subject is willing and able to comply with all trial requirements
* Subject is male or female and over 13 years of age
* Subject has a diagnosis of either TSC or NF1 and has visible fibromatous lesions (angiofibromas or neurofibromas)
* Female subjects of child-bearing potential must not be pregnant and must agree to use appropriate contraceptive methods for the duration of the trial

Exclusion Criteria:

* Subject is currently receiving therapy with rapamycin or sirolimus
* 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 any clinical trial involving an investigational drug
* Subject has a known hypersensitivity to either the PVDF coating (Skincerity®) or rapamycin
* Subject is a pregnant or nursing female
D: Inclusion Criteria:

* Diagnosed with angiomyolipomas and have either Tuberous Sclerosis complex or Lymphangioleiomyomatosis
* Between the gaes of 18 and 65 years
* Competency to voluntarily consent
* Clinically definite diagnosis of tuberous sclerosis or S-LAM
* Adequate contraception
* At least one angiomyolipoma of 1 cm or greater in largest diameter

Exclusion Criteria:

* Use of continuous supplemental oxygen
* Concurrent infection
* Recent surgery
* Ongoing or planned pregnancy
* Lactation
* Use of an investigational drug within the last 30 days of study entrance

Answer: B