Inclusion Criteria:

- Patients must have metastatic histologically or cytologically confirmed uveal
melanoma; 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

- 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 >=
20 mm with conventional techniques or as >= 10 mm with spiral computed tomography
(CT) scan

- Life expectancy > 3 months

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Leukocytes >= 3,000/mm^3

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dL (not requiring transfusions within the past 2 weeks)

- Total bilirubin =< 1.5 times upper limit of normal (ULN); note: patients with
hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin
metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the
treating physician and/or the principal investigator

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 times ULN (=< 5 X institutional ULN for patients with concurrent liver
metastases)

- Creatinine =< 1.5 mg/dL

- Tumor Gnaq and Gna11 status must be determined on all patients using a Clinical
Laboratory Improvement Act (CLIA) approved assay; if initial CLIA testing is
performed locally, patients must consent to provide a tumor block or unstained slides
to Memorial Sloan-Kettering Cancer Center (MSKCC) for central review of Gnaq and
Gna11 status

- Patients must agree to provide all imaging studies for central radiology review

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

- Patients may not be receiving any other investigational agents

- Eligibility for enrollment in each cohort is dependent upon tumor Gnaq/Gna11 status
and prior therapy as follows:

- Cohort 1: no prior TMZ or DTIC; mutant Gnaq/Gna11 status

- Cohort 2: no prior TMZ or DTIC; wild-type Gnaq/Gna11 status

- Cohort 3: received prior TMZ or DTIC; mutant or wild-type Gnaq/Gna11 status

Exclusion Criteria:

- Patients may have had any number of prior therapies, but cannot have previously been
treated with a MEK 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
carmustine (BCNU), mitomycin C or an anti-CTLA4 antibody; patients must have
experienced disease progression on their prior therapy in the opinion of the treating
investigator

- Patients with active or untreated brain 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 TMZ or DTIC or selumetinib (AZD6244)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or bleeding, symptomatic congestive heart failure, unstable angina
pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant women are excluded from this study; breast-feeding should be discontinued if
the mother is treated with AZD6244

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- Note that the AZD6244 manufacturer recommends that adequate contraception for
male patients should be used for 16 weeks post-last dose due to sperm life cycle

- Women of child-bearing potential must have a negative pregnancy test prior to entry

- Known human immunodeficiency virus (HIV)-positive patients on combination
antiretroviral therapy are ineligible

- Patients with compensated HIV, with adequate CD4+ T-cell counts, and not
requiring antiretroviral medication will be allowed

- Patients taking vitamin E supplements while on study

- No concomitant anti-cancer chemotherapy or other systemic drugs; palliative radiation
therapy will be allowed as long as the patient meets all other eligibility criteria

- Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
bowel disease), or significant bowel resection that would preclude adequate
absorption

- Patients with QTc interval > 450 msecs or other factors that increase the risk of QTc
prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history
of long QT interval syndrome) including heart failure that meets New York Heart
Association (NYHA) class III and IV definitions are excluded

- Required use of a concomitant medication that can prolong the QTc interval while
receiving AZD6244; patients who can discontinue medications that prolong the QTc
interval while receiving AZD6244 are eligible