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

Inclusion Criteria

• Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site
• 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 >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI)
• Prior systemic therapies allowed, except for those treatments directed toward, or with activity against, c-Met or vascular endothelial growth factor/receptor (VEGF/R), and the chemotherapy agents temozolomide and dacarbazine; prior treatment must have been no earlier than 3 weeks prior to starting treatment with cabozantinib with exceptions noted below and the following: at least 4 weeks since prior hepatic infusion or at least 2 weeks since radiation therapy
• No cytotoxic chemotherapy including investigational cytotoxic chemotherapy or biologic agents (e.g., cytokines or antibodies) within the last 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment; at least 6 weeks must have elapsed if the last regimen included an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody; patients must have experienced disease progression on their prior therapy in the opinion of the treating investigator
• No prior radiation therapy within the last 4 weeks, except as below
• To the thoracic cavity, abdomen, or pelvis within 12 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery to = 70%)
• A corrected QT interval calculated by the Fridericia formula (QTcF) = 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed; if the average of these three consecutive results for QTcF is = = 0.5 teaspoon (2.5 mL) of red blood within 12 weeks before the first dose of study treatment
• No signs indicative of pulmonary hemorrhage within 12 weeks before the first dose of study treatment
• No prior radiographic evidence of cavitating pulmonary lesion(s)
• No tumor in contact with, invading or encasing any major blood vessels
• No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of treatment
• The patient may not have uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome
• Any of the following within 24 weeks before the first dose of study treatment:
• Unstable angina pectoris
• Clinically-significant cardiac arrhythmias
• Stroke (including transient ischemic attack [TIA], or other ischemic event)
• Myocardial infarction
• Thromboembolic event requiring therapeutic anticoagulation (Note: patients with a venous filter [e.g. vena cava filter] are not eligible for this study)
• 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 muc