Everolimus in Treating Patients with TSC1, TSC2, or Activating MTOR Mutated Cancer That Is Metastatic, Recurrent, or Cannot Be Removed by Surgery

Inclusion Criteria

• Participants must have histologically confirmed advanced malignancy that is metastatic and/or unresectable and/or recurrent with confirmed inactivating mutations in TSC1 or TSC2 or activating MTOR mutations, identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; all genetic findings must be reviewed by the study principal investigator (PI), Dr. David Kwiatkowski, prior to study entry
• Biopsy of a primary or metastatic lesion must have been performed within the past two years; sufficient pathologic material must be available to enable whole exome sequencing at the time of study entry; patients with biopsy samples older than 2 years must undergo a fresh tumor biopsy or should receive approval for enrollment from the principal investigator
• Participants 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, magnetic resonance imaging (MRI), or calipers by clinical exam
• Participants may have received any number of prior therapies, from 0 to > 10; prior treatment with phosphatidylinositol 3 (PI3)-kinase or mTOR inhibitors is not permitted, unless they were given as adjuvant therapy without undue toxicity, and without suggestion of resistance to therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9.0 gr/dL
• Total bilirubin =< 1.5 X the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal; patients with confirmed liver metastases are permitted to have AST/ALT at levels =< 5 X the institutional upper limit of normal (ULN)
• Creatinine =< 1.5 X the institutional upper limit of normal (ULN)
• Total cholesterol < 300 mg/dL
• Triglycerides < 250 mg/dL
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Participants who achieve either a partial response or stable disease >= 4 months must agree to undergo a tumor biopsy, if safe and feasible, at the time of progressive disease while on study drug everolimus

Exclusion Criteria

• Participants who have had any of the following: * Chemotherapy in the previous 2 weeks (6 weeks for nitrosoureas or mitomycin C) * Radiotherapy within 3 weeks * Investigational agents within 3 weeks prior to entering the study * Patients who have not recovered from significant (in the opinion of the investigator) adverse events due to previous agents administered
• Child-Pugh B or C hepatic impairment; patients with a history of hepatitis or significant exposure risk should be tested for hepatitis B and C with serologic markers: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBs Ab), hepatitis B core immunoglobulin G antibody (HBcoreIgG Ab), hepatitis C virus antibody (HCV Ab); patients with active hepatitis B or C are excluded
• Participants may not be receiving any other research study agents
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases; asymptomatic or treated brain metastases are acceptable
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus
• A list of prohibited medications on study are listed
• Chronic treatment with corticosteroids or other immunosuppressive therapy
• 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 everolimus
• Individuals with a recent history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years OR are deemed by the investigator to be at low risk for recurrence of that malignancy; 2) individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
• Individuals with known human immunodeficiency virus (HIV) infection are excluded from this study
• Patients who have received live attenuated vaccines within 1 week of start of everolimus; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Uncontrolled diabetes mellitus: hemoglobin A1c (HbA1c) must be < 8% or there must be documentation that control has been good for the week prior to study entry, with daily morning glucoses at < 150 mg/dl; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary