RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma

Inclusion Criteria

• Patients must have histologically or cytologically confirmed metastatic uveal melanoma.
• 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) as > or = to 20 mm with conventional techniques or as > or = to 10 mm with spiral CT scan.
• Patients may have had any number of prior therapies, but cannot have previously been treated with a somatostatin analogue or an mTOR inhibitor. At least 3 weeks must have elapsed since the last dose of systemic therapy. At least 6 weeks must have elapsed if the last regimen included BCNU or mitomycin C. At least 3 months must have elapsed if the last regimen included an anti-CTLA4 antibody. If the last regimen included an anti-CTLA4 antibody, radiographic disease progression since this therapy must be documented.
• Age > or = to 18 years. Because no dosing or adverse event data are currently available on the use of RAD001 and SOM230 in patients or = to 3,000/mcL
• absolute neutrophil count > or = to 1,500/mcL
• platelets > or = to 100,000/mcL
• hemoglobin > or = to 9.0 g/dL not requiring transfusions within the past 2 weeks
• total bilirubin 2 weeks at time of study initiation).
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Ability to understand and the willingness to sign a written informed consent document.
• Evidence of disease progression, as determined by the investigator.

Exclusion Criteria

• Patients may not be receiving any other investigational agents.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated brain metastases must have been stable for at least 2 months.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or SOM230.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or bleeding, severely impaired lung function, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because RAD001 and SOM230 are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, breast-feeding should be discontinued.
• Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot). The safety of a potentially immunosuppressive drug like everolimus is not proven in patients with HIV. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection (see Section 8.0 and hepatitis B/C risk factor screening form.
• Baseline QTc > 450 ms.
• Patients with risk factors for torsades de pointes, including uncorrected hypokalemia, uncorrected hypomagnesemia, family history of long QT syndrome, clinically significant/symptomatic bradycardia, high-grade AV block, autonomic neuropathy (including that caused by diabetes or Parkinson's disease, uncontrolled hypothyroidism, cirrhosis, or the use of concomitant medications known to prolong the QT interval.
• Patients with a history of syncope, family history of idiopathic sudden death, a history of sustained or clinically significant cardiac arrhythmias, symptomatic congestive heart failure (NYH