Temsirolimus/AZD 6244 for Treatment-naive With BRAF Mutant Unresectable Stage IV
Condition: Mucosal Melanoma; Recurrent Melanoma; Stage IV Melanoma
MeSH terms: Melanoma
Intervention: temsirolimus; selumetinib; laboratory biomarker analysis
Intervention description: Given IV; Given orally; Correlative studies
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to find out how often two investigational drugs that are given
      together will shrink the patient's tumor and how well they will prolong the time it takes
      their tumor to grow. The investigators also wish to find out how they affect certain
      substances in the patient's tumor and in their blood important for tumor growth. The
      combination of these drugs is experimental, and has not been proven to help treat melanoma
    

Eligibility criteria:

        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