Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV

Inclusion Criteria:

* Subject must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained
* Subjects with a histologic diagnosis of unresectable stage IV melanoma (may include mucosal melanoma)
* Tumor must be BRAF V600E mutation positive from a certified lab
* At least 4 weeks since any previous treatment (surgery, radiotherapy, or systemic treatment)
* Women should be either: post-menopausal for at least 1 year; surgically incapable of bearing children; or utilizing a reliable form of contraception during the study and for at least 4 months after the final study drug infusion or ingestion; women of childbearing potential must have a negative serum hCG-beta pregnancy test conducted during the screening period
* Men who may father a child must agree to the use of male contraception for the duration of their participation in the trial and for at least 4 months after the final temsirolimus and AZD6244 hydrogen sulfate administration
* Life expectancy \>= 3 months
* ECOG performance status of 0 or 1
* Patients with brain metastases treated with surgery, radiation, or stereotactic radiosurgery who are without evidence of progression in their brain metastases after MRI imaging performed at least 30 days after treatment, and are not taking systemic steroids will be eligible
* WBC \>= 3000 cells/mm\^3
* ANC \>= 1500 cells/mm\^3
* Platelets \>= 100,000/mm\^3
* Hematocrit \>= 30%
* Hemoglobin \>= 9 g/dL
* Creatinine =\< 2.0 mg/dL
* AST/ALT =\< 2 x ULN
* Bilirubin =\< 1.5 x ULN, (except subjects with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL)
* HIV negative
* HBsAg negative
* Anti-HCV Ab nonreactive; if reactive, subject must have a negative HCV RNA qualitative PCR
* Patients with hyperlipidemia must have adequate control with a lipid lowering agent

Exclusion Criteria:

* Any prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer from which the subject has been disease-free for at least 5 years
* Active infection, requiring therapy, chronic active HBV or HCV; patients with HIV, who have adequate CD4 counts and who do not require HAART therapy, are NOT excluded
* Pregnancy or nursing: due to the possibility that temsirolimus and AZD6244 hydrogen sulfate could have a detrimental effect on the developing fetus or infant, exposure in utero or via breast milk will not be allowed
* Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events
* Prior treatment with temsirolimus or AZD6244 or any prior mTOR or MEK inhibitor
* Evidence or history of significant cardiac, pulmonary, hepatic, renal, psychiatric or gastrointestinal disease that would make the administration of temsirolimus or AZD6244 hydrogen sulfate unsafe
* Tumor that is BRAF V600E mutation negative