Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus
Condition: Sporadic Angiomyolipomas (AMLs)
MeSH terms: Angiomyolipoma
Intervention: Everolimus
Intervention description: 10 mg tablets
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to see if oral everolimus is tolerable and effective in
      the treatment of sporadic Angiomyolipomas (AMLs). AMLs are the most common non-cancerous
      tumor of the kidney. They are composed of blood vessels, muscle cells and fat
      cells.Everolimus is already an approved drug for several other diseases like kidney cancer,
      but is being studied now specifically to see if it is helpful for people with AML.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have a diagnosis of renal AML > 3 cm confirmed on pre-enrollment Dynamic Contrast
             Enhanced MRI (DCE-MRI)

          -  Must not have received any prior treatment for AML

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

          -  Absolute neutrophil count >= 1,500/ microliter (mcL)

          -  Hemoglobin >=10 g/dL

          -  Platelets >= 100,000/ mcL

          -  international normalized ratio (INR) <= 1.2 X Upper limit Normal (ULN)

          -  activated partial thromboplastin time (aPTT) <= 1.2 X ULN

          -  aspartate aminotransferase (AST) / alanine transaminase (ALT) <= 2.5 X ULN

          -  Total bilirubin <= 2.0mg/dL

          -  Renal Function epidermal growth factor receptor (eGFR) >= 30 mL/min via calculated
             creatinine clearance

          -  Fasting serum cholesterol <= 300 mg/dL OR <= 7.75 mmol/L AND fasting triglycerides <=
             2.5x ULN.

        Exclusion Criteria:

          -  History of tuberous sclerosis, LAM or any active malignancy

          -  Treatment with any other investigational agents for any other disease

          -  Clinically significant gastrointestinal abnormalities that may increase the risk for
             gastrointestinal bleeding or affect absorption of investigational product

          -  Active diarrhea of any grade.

          -  History of human immunodeficiency virus (HIV) infection, hepatitis B or C (screening
             for all three is mandatory prior to study); prior hepatitis C infection

          -  Presence of any active or ongoing infection.

          -  Any known uncontrolled underlying pulmonary disease by history, physical exam or if
             applicable pulmonary function test (PFTs)

          -  History of certain cardiovascular conditions within the past 6 months

          -  History of Class III or IV congestive heart failure, as defined by the New York Heart
             Association Classification of Congestive Heart Failure.

          -  History of cerebrovascular accident including transient ischemic attack (TIA),
             pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

          -  Corrected QT interval (QTc) > 480 milliseconds

          -  Poorly controlled hypertension, defined as systolic blood pressure (SBP) of >= 140
             millimeters of mercury(mmHg) or diastolic blood pressure (DBP) of >= 90 mmHg.

          -  Evidence of active bleeding or bleeding diathesis

          -  Uncontrolled diabetes mellitus (defined by a Hgb A1c >8) obtained within 14 days prior
             to registration. Optimal glucose control (Hgb A1c <= 8) must be achieved before
             registration and monitored during protocol treatment

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures.

          -  Unable or unwilling to discontinue use of prohibited medications

          -  Concurrent therapy given to treat cancer including treatment with an investigational
             agent or concurrent participation in another clinical trial involving anti-cancer
             investigational drug.

          -  Administration of any investigational drug within 30 days or 5 half-lives, whichever
             is longer, preceding the first dose of study treatment.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to everolimus

          -  Prior or current use of systemic anti-vascular endothelial growth factor (VEGF)
             inhibitors, cytokines or mechanistic target of rapamycin (mTOR) inhibitors (e.g.
             interferon, interleukin 2).

          -  Pregnant or nursing (lactating) women

          -  Women of child-bearing potential (WOCBP) must use highly effective methods of
             contraception during the study and 8 weeks after.

          -  Unable to obtain a contrast (gadolinium) based DCE MRI, including include patients
             with pacemakers, automatic implantable cardioverter/defibrillator (AICDs), non MRI
             compatible metallic implants or eGFR <30.

          -  Must not have received immunization with an attenuated live vaccine within seven days
             prior to registration nor have plans to receive such vaccination while on protocol
             treatment

          -  Must not be taking, nor plan to take while on protocol treatment, strong cytochrome
             P450 3A4 (CYP3A4) inhibitors, (e.g. ketoconazole, itraconazole, voriconazole,
             posaconazole, fluvoxamine, nefazodone, nelfinavir, ritonavir) and/or strong CYP3A4
             inducers (e.g. phenytoin, rifampin, rifabutin) within 14 days prior to randomization.

          -  History of another primary malignancy, with the exceptions of: non-melanoma skin
             cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient
             has been disease free for >= 3 years

          -  Childs-Pugh A-C liver disease (Appendix II)