Please select the eligibility criteria that correspond to the clinical trial below.
Title: Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex and Neurofibromatosis 1
Brief Summary: This study is a prospective, randomized, double-blind, placebo-controlled evaluation of the safety of a topically applied formulation of rapamycin to cutaneous fibromatous lesions in subjects with Tuberous Sclerosis Complex (TSC) and Neurofibromatosis I (NF1). Subjects will apply either a Polyvinylidene fluoride (PVDF) coating (Skincerity) containing rapamycin or the PVDF coating alone nightly to fibromatous lesions for a duration of six months.

The primary goal of this study is to evaluate the safety of the topical product in patients with TSC and NF1. The secondary goal of this study is to evaluate the effectiveness of the topical product for treatment of cutaneous fibromatous lesions.


Options:
A: 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.
B: 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
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:

* 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

Answer: C