Akt Inhibitor MK2206 or Everolimus in Treating Patients With Refractory Kidney Cancer
Condition: Metastatic Kidney Carcinoma; Recurrent Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Akt Inhibitor MK2206; Everolimus; Laboratory Biomarker Analysis
Intervention description: Given PO; Given PO; Optional correlative studies
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the side effects and how well Akt inhibitor MK2206 or
      everolimus works in treating patients with kidney cancer that does not respond to treatment.
      Akt inhibitor MK2206 and everolimus may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth. Everolimus may also stop the growth of kidney cancer by
      blocking blood flow to the tumor. It is not yet known whether Akt inhibitor MK2206 or
      everolimus is more effective in treating kidney cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed metastatic or
             unresectable RCC; all histologies are permitted; patient should have undergone
             nephrectomy

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography (CT) scan

          -  Patients must have received, and progressed on an anti-VEGF therapy, including
             bevacizumab, 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 x
             ULN; therapeutic anticoagulation with warfarin is allowed if target INR =< 3 on a
             stable 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 (hormonal
             or barrier method of birth control; abstinence) prior to study entry, for the duration
             of study participation and for 8 weeks after the last dose of study drug; should a
             woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, the patient should inform the treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Serum pregnancy test in female patients of childbearing potential must be negative
             within 24 hours of enrolling on this study

        Exclusion Criteria:

          -  Patients who received oral tyrosine-kinase inhibitors (TKIs) (sorafenib, sunitinib, or
             pazopanib) within 2 weeks prior to entering the study, radiotherapy, immunotherapy or
             chemotherapy within 4 weeks prior to entering the study, bevacizumab within 4 weeks
             prior to entering the study, or those who have not recovered from adverse events due
             to agents administered more than 4 weeks earlier (recovered to =< grade 1)

          -  Patients may not be receiving any other investigational agents; patients may not have
             received 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 biologic
             composition to MK-2206 or other agents used in the study

          -  Patients receiving any medications or substances that are strong inhibitors or
             inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP4503A4) are
             ineligible

          -  Patient should have a hemoglobin A1C value of < 8%; preclinical studies demonstrated
             the potential of MK-2206 for induction of hyperglycemia in all preclinical species
             tested; studies also demonstrate a risk of hyperglycemia, hyperlipidemia and
             hypertriglyceridemia associated with everolimus therapy; patients with diabetes or in
             risk for hyperglycemia, hyperlipidemia and/or hypertriglyceridemia should not be
             excluded from trials with MK-2206 or everolimus, but the patient should be well
             controlled 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 active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with MK-2206 or everolimus

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Individuals who are diagnosed with an intercurrent cancer are excluded, with the
             exception of non-melanoma skin cancers, and other cancers where curative treatment was
             completed at least two years ago