Cabozantinib-S-Malate Compared With Temozolomide or Dacarbazine in Treating Patients With Metastatic Melanoma of the Eye That Cannot Be Removed by Surgery

* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:

* Any of the following within 28 days before the first dose of study treatment

* Intra-abdominal tumor/metastases invading GI mucosa

* Active peptic ulcer disease

* Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis

* Malabsorption syndrome

* Any of the following within 24 weeks before the first dose of study treatment:

* Abdominal fistula

* Gastrointestinal perforation

* Intra-abdominal abscess; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 24 weeks before the first dose of study treatment

* Bowel obstruction or gastric outlet obstruction

* Other clinically significant disorders such as:

* Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment

* History of organ transplant

* Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment

* History of major surgery as follows:

* Major surgery in past 8 weeks of the first dose of cabozantinib if there were no wound healing complications or within 24 weeks of the first dose of cabozantinib if there were wound complications

* Minor surgery within 4 weeks of the first dose of cabozantinib if there were no wound healing complications or within 12 weeks of the first dose of cabozantinib if there were wound complications

* In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

* Active infection requiring systemic treatment within 28 days before the first dose of study treatment

No concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=\< 81 mg/day), low-dose warfarin (=\< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted; please note that drugs that strongly induce or inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or are associated with a risk of Torsades are not allowed; chronic concomitant treatment of CYP3A4 inducers is not allowed (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the following drugs are strong inhibitors of CYP3A4 and are not allowed during the treatment with cabozantinib:

* Boceprevir

* Indinavir

* Nelfinavir

* Lopinavir/ritonavir

* Saquinavir

* Telaprevir

* Ritonavir

* Clarithromycin

* Conivaptan

* Itraconazole

* Ketoconazole

* Mibefradil

* Nefazodone

* Posaconazole

* Voriconazole

* Telithromycin

* Drugs with possible or conditional risk of torsades should be used with caution knowing that cabozantinib could prolong the QT interval

* Any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea \>= 12 consecutive months)

* Women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level \> 35m IU/mL

* Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)

No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, temozolomide and dacarbazine

Absolute neutrophil count \>= 1,500/mcL

Platelets \>= 100,000/mcL

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

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5.0 × institutional upper limit of normal (for patients with metastases); AST (SGOT)/ALT (SGPT) =\< 2.5 × institutional upper limit of normal (for patients without metastases)

Serum creatinine =\< 1.5 × ULN, OR calculated creatinine clearance \>= 30 mL/minute (modified Cockcroft and Gault formula)

Hemoglobin \>= 9 g/dL

Serum albumin \>= 2.8 g/dL

Urine protein/creatinine ratio (UPCR) =\< 1; if urine/protein creatinine (UPC) \>= 1, then a 24-hour urine protein must be assessed; eligible patients must have a 24-hour urine protein value \< 1 g/L

Thyroid-stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH however free T4 and free thyroxine index (FTI) are normal and patient is clinically euthyroid, patient is eligible

Prothrombin time (PT)/international normalized ratio (INR) must be =\< 1.2 x the laboratory ULN

No clinical or radiographic evidence of pancreatitis

What this study is about