Study of Dabrafenib, Trametinib and Metformin for Melanoma Patients

Inclusion Criteria:

Male or female patients > 18 years of age
Patients with histologically confirmed BRAFV600E melanoma (Stage IIIC or
Stage IV, American Joint Commission on Cancer)
Eastern Cooperative Oncology Group Performance Status of 0 to 2
Life expectancy > 3 months
At least 1 site of radiographically measurable disease by RECIST 1.1
Adequate hematologic, renal, and liver function as defined by laboratory values performed within 42 days prior to initiation of dosing:
Absolute neutrophil count > 1.0 x 10⁹/L
Platelet count > 50 x 10⁹/L
Hemoglobin > 8 g/dL
Serum creatinine < 2 x upper limit of normal
Total serum bilirubin < 3 x ULN
Serum aspartate transaminase or serum alanine transaminase < 3 x ULN, and < 4 x ULN if liver metastases are present
Fertile males should use an effective method of contraception during treatment and for at least 3 months after completion of treatment, as directed by their physician
Pre-menopausal females and females < 2 years after the onset of menopause should have a negative pregnancy test at Screening. Pre-menopausal females must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 90 days after the last dose of the study drug
Females of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for > 1 year
Before study entry, written informed consent must be obtained from the patient prior to performing any study related procedures

Exclusion Criteria:

Prior treatment with Vemurafenib or Dabrafenib
Known hypersensitivity to Metformin or any of its components
Received radiotherapy for non CNS disease within the 2 weeks prior to commencing study treatment or have not recovered from side effects of all radiation related toxicities to Grade < 1, except for alopecia
Pregnant, breast feeding, or refusing double barrier contraception, oral contraceptives, or avoidance of pregnancy measures
Have any other uncontrolled infection or medical condition that could interfere with the conduct of the study