Everolimus for Cancer With TSC1 or TSC2 Mutation

Inclusion Criteria: Participants must meet the following criteria on screening examination to be eligible to participate in the study: * Participants must have histologically confirmed advanced malignancy that is either metastatic and/or unresectable and/or recurrent, with confirmed inactivating mutations in TSC1 or TSC2, or activating mutations in MTOR, identified in any CLIA-certified laboratory. All genetic findings must be reviewed by the study 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. * 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) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease. * Participants may have received any number of prior therapies, from 0 to \> 10, but prior treatment with PI3-kinase or mTOR inhibitors is not permitted. * Age ≥ 18 years. * ECOG performance status \<2 (see Appendix A). * Participants must have normal organ and marrow function as defined below: * Leukocytes ≥3,000/mcL * Absolute neutrophil count ≥1,500/mcL * Platelets ≥100,000/mcL * Hemoglobin ≥9.0 gr/dL * Total bilirubin ≤1.5 ULN * AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal. Patients with confirmed liver metastases are permitted to have AST/ALT at levels ≤ 5X the institutional upper limit of normal. * Creatinine ≤ 1.5 X the institutional upper limit of normal. * Total cholesterol \< 300 mg/dL * Triglycerides \< 250 mg/dL * The effects of everolimus on the developing human fetus are unknown. For this reason and because anti-neoplastic agents are known to be teratogenic, 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 exhibit any of the following conditions at screening will not be eligible for admission into the study. * 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: HBsAg, HBs Ab, HBcoreIgG Ab, HCV Ab. Patients with active hepatitis B or C are excluded. * Any prior exposure to any PI3 kinase or mTOR inhibitor agent. * 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 in Section 5.5 * 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 because everolimus has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with everolimus, breastfeeding should be discontinued if the mother is treated with everolimus. These potential risks may also apply to other agents used in this study. * 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 HIV infection are excluded from this study as combination antiretroviral therapy could potentially result in significant pharmacokinetic interactions with everolimus. In addition, these individuals are at increased risk of lethal infections due to the immunosuppressive effects of mTOR inhibition. * 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, BCG, yellow fever, varicella and TY21a typhoid vaccines. * Uncontrolled diabetes mellitus as defined by HbA1c \>8% despite adequate therapy. 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.