Ensayos clínicos

Inclusion Criteria

• Must have a diagnosis of renal angiomyolipomas > 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 must use highly effective methods of contraception during the study and 8 weeks after
• Unable to obtain a contrast (gadolinium) based DCE MRI, includes patients with pacemakers, automatic implantable cardioverter/defibrillators (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