Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer

Inclusion Criteria:

* Have low grade UTUC undergoing nephroureterectomy or ureterectomy, or high grade UTUC and not eligible for cis-platin neoadjuvant chemotherapy either due to medical comorbidities (e.g., cardiac dysfunction, hearing loss, glomerular filtration rate \[GFR\] \< 50), or based on \< 49% risk prediction of non-organ confined disease by clinical nomogram
* Have adequate biopsy tissue available for mutational analysis, as determined by the study pathologist, prior to enrollment. Any biopsy of index UTUC tissue available within 6 weeks of enrollment may be used
* Calculated or measured creatinine clearance \>= 30 mL/min
* Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Are able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
* Have recovered from AEs of previous systemic anti-cancer therapies to baseline or grade 1, except for alopecia
* Are able to swallow and retain oral medication
* Are willing and able to comply with scheduled visits, treatment plan and laboratory tests
* If a woman of childbearing potential (WOCBP), must have a negative pregnancy test within 7 days of the first dose of study drug. A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study drug) or if she is post-menopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (e.g., hormonal therapy, prior chemotherapy). WOCBP and males whose sexual partners are WOCBP must agree to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group, 2014) while receiving study drug and for 3 months following their last dose of study drug. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Sexually active males must use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child during this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid

Exclusion Criteria:

* Have a history of another primary malignancy within 3 years except:

  * Adequately treated in situ carcinoma of the cervix, non-melanoma carcinoma of the skin
  * Any other untreated cancer deemed by treating physician to be at low risk for progression during the study period (such as low or intermediate risk prostate cancer)
  * Curatively treated malignancy that is not expected to have recurrence or require treatment during the course of the study
* Have uncontrolled bladder cancer. Patients with bladder cancer must have bladder cleared of disease by transurethral resection prior to initiating treatment and must not be at need for systemic therapy
* Have any other medical condition that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures
* Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination. Subjects with asymptomatic ophthalmologic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study
* Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vasculature and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
* Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
* Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc
* Are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone
* Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug
* Have used medications known to prolong the QT interval and/or are associated with a risk of torsades de pointes (TdP) 7 days prior to first dose of study drug
* Have used amiodarone within 90 days prior to first dose of study drug
* Are currently using therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulants or using direct thrombin inhibitors (e.g., argatroban) or factor Xa inhibitors (e.g., rivaroxaban) that are primarily metabolized by CYP3A4. Heparin and/or low molecular weight heparins or direct thrombin inhibitors and/or factor Xa inhibitors that are not metabolized by CYP3A4 (e.g., dabigatran, edoxaban) are allowed
* Absolute neutrophil count (ANC) \< 1,000/mm\^3 (1.0 x 10\^9/L)
* Platelets \< 100,000/mm\^3 (75 x 10\^9/L)
* Hemoglobin \< 9.0 g/dL
* Total bilirubin \> 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
* Aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) \> 2.5 x ULN (AST and ALT \> 5 x ULN in the presence of liver involvement of cholangiocarcinoma)
* Calculated or measured creatinine clearance of \< 30 mL/min
* Have amylase or lipase \> 2.0 x ULN
* Have abnormal calcium-phosphate homeostasis:

  * Inorganic phosphorus outside of local normal limits
  * Total corrected serum calcium outside of local normal limits
* Have clinically significant cardiac disease including any of the following:

  * Congestive heart failure requiring treatment (New York Heart Association grade \>= 2), left ventricular ejection fraction (LVEF) \< 50% or local lower limit of normal as determined by echocardiogram (ECHO), or uncontrolled hypertension
  * Presence of Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 or later grade \>= 2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality
  * Unstable angina pectoris or acute myocardial infarction =\< 3 months prior to first dose of study drug
  * Corrected QT interval by Fridericia (QTcF) \> 470 msec (males and females)

    * Note: If the QTcF is \> 470 msec in the first electrocardiography (ECG), a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is =\< 470 msec, the subject meets eligibility in this regard
  * Known history of congenital long QT syndrome
* Have had a recent (=\< 3 months) transient ischemic attack or stroke