RAPAMYCIN FOR KIDNEY ANGIOMYOLIPOMAS
Condition: Nonmalignant Neoplasm; Tuberous Sclerosis; Lymphangioleimyomatosis; Kidney Angiomyolipoma
MeSH terms: Tuberous Sclerosis; Angiomyolipoma
Intervention: Rapamycin
Intervention MeSH terms: Sirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 3 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: angiomyolipoma

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.
    

Eligibility criteria:

        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.