A Phase 2 Study of XL184 (Cabozantinib) in Recurrent or Metastatic Endometrial Cancer

• Patients must have histologically or cytologically confirmed metastatic endometrial cancer; eligible histologies for the experimental cohort are: endometrioid or serous; eligible histologies for the exploratory cohort are: carcinosarcoma, clear cell, mixed, adenosquamous and any other rare sub-type of endometrial cancer

• 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 \>= 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam and \>= 15 mm in short axis for nodal lesions; patients must have radiographic evidence of disease progression following the most recent line of treatment

• Prior therapy: Eligible subjects must have had 1 line of systemic cytotoxic treatment; this may be adjuvant therapy with documented progression within 12 months of completion, or 1 line of cytotoxic therapy for metastatic disease; NOTE: eligible patients are allowed up to 2 lines of systemic cytotoxic treatment, of which only 1 line is allowed for metastatic disease; the acceptance of progression within 12 months of adjuvant is part inclusion to not require patient to re-challenge with chemotherapy (chemo) if they progressed soon after adjuvant therapy; prior hormonal therapy for metastatic/recurrent disease is also allowed; prior targeted therapy not directed against cMET or vascular endothelial growth factor (VEGF) pathways is allowed

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

• Life expectancy of greater than 3 months

• Absolute neutrophil count \>= 1.5 x 10\^9/L

• Platelets \>= 100 x 10\^9/L

• Total bilirubin =\< 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 X institutional upper limit of normal

• Creatinine =\< 1.5 x ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal

• Hemoglobin \>= 90 g/L

• Serum albumin \>= 28 g/L

• Lipase \< 2.0 x ULN; no radiologic/clinical evidence of pancreatitis

• Urine protein/creatinine ratio (UPCR) =\< 1

• Serum phosphorus, calcium, magnesium and potassium \>= lower limit of normal (LLN)

• Women of childbearing potential must have a negative pregnancy test at screening; women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal; postmenopausal is defined as amenorrhea \>= 12 consecutive months; note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason

• Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; sexually active subjects must agree to use medically accepted barrier methods of contraception (e.g., male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)

• Patients must consent to analysis on archival tissue; if archival sample is not available, a sufficient tumor biopsy can be performed a minimum of 28 days prior to start of treatment if felt to be clinically reasonable

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