Selumetinib in Cancers With BRAF Mutations
Condition: Adult Solid Neoplasm
Intervention: Selumetinib
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this research study is to determine if selumetinib is safe and effective in
      treating patients with cancers with a mutated BRAF gene. Selumetinib is an investigational
      drug that works by blocking a protein called MEK, which is known to play a role in the growth
      of cancer cells lines and tumors that have a mutated BRAF gene. There are multiple types of
      cancers that have mutations in the BRAF gene and depend on the activity of this gene for
      their growth and survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and willingness to sign a written informed consent document

          -  Histologically confirmed metastatic or unresectable solid tumor

          -  Results from tumor tissue analysis that show a glutamic acid-for-valine substitution
             at amino acid position 600 in the BRAF gene (V600E) or other activating BRAF mutation,
             as determined by high-throughput genotyping

          -  Patients may have received any number of prior systemic treatments for their cancer

          -  At least one measurable site of disease by CT, according to standard RECIST criteria
             1.0

          -  ECOG performance status 0-1

          -  Absolute neutrophil count > 1500 per cubic mm

          -  Platelet count > 100,000 per cubic mm

          -  Hemoglobin > 9 g/dl

          -  Serum bilirubin < 1.5 x upper limit of normal

          -  Serum AST and ALT < 2.5 x upper limit of normal (=< 5 x upper limit of normal, for
             liver metastases)

          -  Serum creatinine < 1.5 x upper limit of normal

          -  For women of childbearing potential, negative serum pregnancy test and use of
             physician-approved method of birth control throughout the study

        Exclusion Criteria:

          -  Estimated life expectancy > 12 weeks

          -  Patients with melanoma

          -  Have received chemotherapy or radiotherapy within 4 weeks prior to entering the study
             (6 weeks for nitrosoureas or mitomycin C), or a targeted therapy within 2 weeks prior
             to entering the study

          -  Have not recovered from adverse events due to agents previously administered (CTCAE v3
             grade 1 or baseline)

          -  Currently receiving other investigational agents

          -  Known brain metastases, unless treated and stable off of corticosteroids for at least
             four weeks

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AZD6244

          -  Prior treatment with a selective inhibitor of RAF or MEK (e.g., RAF265); (note: prior
             sorafenib is allowed)

          -  Uncontrolled intercurrent illness, including but not limited to:

               -  Clinically significant active infection

               -  Symptomatic congestive heart failure, unstable angina pectoris, and/or cardiac
                  arrhythmia other than atrial fibrillation

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  Refractory nausea or vomiting, swallowing disorder, or malabsorption syndrome that
             would interfere with swallowing or absorbing the study medication

          -  Pregnant and/or breast-feeding women

          -  Previous or concurrent malignancy, except for the following circumstances:

               -  Disease-free for at least three years and deemed by investigator to be at low
                  risk for recurrence of that malignancy

               -  Individuals with the following cancers are eligible if diagnosed and treated
                  within the past 5 years: cervical cancer in situ, and basal cell or squamous cell
                  carcinoma of the skin)

          -  History of solid organ transplantation or other condition requiring the use of
             immunosuppressive medications

          -  Uncontrolled hypertension (systolic BP >= 150 or diastolic BP >= 100 that cannot be
             controlled with medications)

          -  A mean left ventricular ejection fraction (LVEF) less than 45%