Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations

Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Must have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastatic

Patient must have TCCs tumors harboring a TSC1 or TSC2 mutation identified by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory

Unless the pre-screening was performed at Yale Clinical Molecular Pathology Lab (YCMPL), patients must have TCC tumor tissue available for submission in a form of at least 10 unstained slides or formalin-fixed paraffin-embedded (FFPE) block (FFPE block highly recommended and preferred) along with a buccal swab; if the number of slides is less than 10, a biopsy should be considered; if a biopsy is deemed unsafe, the case may be discussed with the study principal investigator (PI) and approval must be given for eligibility

Patient must have developed disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine/cisplatin \[GC\], methotrexate-vinblastine-doxorubicin-cisplatin \[MVAC\], carboplatin, gemcitabine \[CarboGem\]) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or must be unfit or ineligible for cisplatin-based chemotherapy; there is no restriction on the number of prior lines of chemotherapeutics agents received

* Patients who progressed within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant regimen are considered second-line patients; therefore, these patients may be also eligible

* Patients who are unfit or ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria are eligible for this trial:

* Eastern Cooperative Oncology Group (ECOG) performance score of 2

* Creatinine clearance \< 60 mL/min

* A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies

* Grade \>= 2 peripheral neuropathy

ECOG performance status =\< 2 (Karnofsky \>= 60 %)

Life expectancy of greater than 12 weeks

Hemoglobin \>= 9 g/dL

Fasting serum glucose =\< 130 mg/dL

Glycosylated hemoglobin measurement (HbA1c) \< 7.0%

Fasting triglycerides =\< 300 mg/dL

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 (ULN) and =\< 5 ULN if liver metastases are present

Creatinine =\< 1.5 x upper normal institutional limits (UNL) OR creatinine clearance \>= 40 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour)

Patients with controlled diabetes are allowed on study; controlled diabetes is defined as fasting blood sugar (FBS) = 130 mg/dL or less, and patients whose FBS can be brought in this range with medical therapy are eligible for trial inclusion

The effects of MLN0128 (TAK-228) on the developing human fetus are unknown; fertility and developmental studies with MLN0128 (TAK-228) have not been conducted; on the basis of potential hazard of other mTOR inhibitors (i.e., rapamycin and other rapalogs) on the developing fetus, women of childbearing age should avoid becoming pregnant while taking any mTOR inhibitor including MLN0128 (TAK-228)

* Female patients must:

* Be postmenopausal for at least 1 year before the screening visit, OR

* Be surgically sterile, OR

* If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling \[e.g., United States product insert \[USPI\], summary of product characteristics \[SmPC\], etc.;\]) after the last dose of study drug, OR

* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient; NOTE: periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together

* Male patients, even if surgically sterilized (i.e., status postvasectomy), must:

* Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR

* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (NOTE: periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception; female and male condoms should not be used together)

* AND agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug

Ability to swallow oral medications

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

What this study is about