Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic orunresectable RCC; all histologies are permitted; patient should have undergonenephrectomy

• Patients must have measurable disease, defined as at least one lesion that can beaccurately measured in at least one dimension (longest diameter to be recorded fornon-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventionaltechniques or as >= 10 mm with spiral computed tomography (CT) scan

• Patients must have received, and progressed on an anti-VEGF therapy, includingbevacizumab, sorafenib, sunitinib or pazopanib

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

• Serum creatinine =< 1.5 x upper limit of normal (ULN)

• International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 xULN; therapeutic anticoagulation with warfarin is allowed if target INR =< 3 on astable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks at time of randomization

• Women of childbearing potential and men must use two forms of contraception (hormonalor barrier method of birth control; abstinence) prior to study entry, for the durationof study participation and for 8 weeks after the last dose of study drug; should awoman become pregnant or suspect she is pregnant while she or her partner isparticipating in this study, the patient should inform the treating physicianimmediately

• Ability to understand and the willingness to sign a written informed consent document

• Serum pregnancy test in female patients of childbearing potential must be negativewithin 24 hours of enrolling on this study

Exclusion Criteria:

• Patients who received oral tyrosine-kinase inhibitors (TKIs) (sorafenib, sunitinib, orpazopanib) within 2 weeks prior to entering the study, radiotherapy, immunotherapy orchemotherapy within 4 weeks prior to entering the study, bevacizumab within 4 weeksprior to entering the study, or those who have not recovered from adverse events dueto agents administered more than 4 weeks earlier (recovered to =< grade 1)

• Patients may not be receiving any other investigational agents; patients may not havereceived an mammalian target of rapamycin (mTOR) inhibitor

• Patients with known brain metastases should be excluded from this clinical trial

• History of allergic reactions attributed to compounds of similar chemical or biologiccomposition to MK-2206 or other agents used in the study

• Patients receiving any medications or substances that are strong inhibitors orinducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP4503A4) areineligible

• Patient should have a hemoglobin A1C value of < 8%; preclinical studies demonstratedthe potential of MK-2206 for induction of hyperglycemia in all preclinical speciestested; studies also demonstrate a risk of hyperglycemia, hyperlipidemia andhypertriglyceridemia associated with everolimus therapy; patients with diabetes or inrisk for hyperglycemia, hyperlipidemia and/or hypertriglyceridemia should not beexcluded from trials with MK-2206 or everolimus, but the patient should be wellcontrolled on oral agents (recent [i.e. within 3 months] hemoglobin [Hb]A1C =< 7.0)before the patient enters the trial

• Baseline corrected Fridericia QT interval (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements

• Pregnant women are excluded from this study; breastfeeding should be discontinued ifthe mother is treated with MK-2206 or everolimus

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviraltherapy are ineligible

• Individuals who are diagnosed with an intercurrent cancer are excluded, with theexception of non-melanoma skin cancers, and other cancers where curative treatment wascompleted at least two years ago