Sporadic Angiomyolipomas (AMLs) Growth Kinetics While on Everolimus (SAGE)

This is an interventional treatment trial for Sporadic Angiomyolipomas (AMLs) Read More

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)