Ipilimumab and Dabrafenib in the 1st Line Tx of Unresectable Stage III/IV Melanoma

Who may be able to join

• For Phase I: Locally advanced or metastatic BRAF V600E/K/R positive melanoma that is either treatment-naïve or treatment-experienced. For the latter, progression, or stable as best response, or intolerance to the last treatment is required. Previous treatments can be local or systemic therapies. There are no limits to the number of prior therapies. For all patients, disease does not have to be measurable but must be evaluable, which is defined as one or more lesions which are known to be present, but which cannot be measured. eg: Bony lesions, pleural effusion, ascites.
• For Phase I: For treatment-experienced patients, the following washout periods are required prior to enrollment on the study: 2 weeks wash out after prior local therapy (such as radiation therapy or intra-lesional therapy), 4 weeks wash out after cytotoxic therapy or high dose interleukin-2, and 6 weeks wash out after anti-PD-1 or anti-PD-L1 therapy. For all other therapy not mentioned, a wash out period of at least 5 half lives will be needed.
• For phase II: Histological diagnosis of BRAF V600E/K melanoma, unresectable stage III or stage IV, according to the AJCC Staging Manual, 7th Edition, 2011. Must have measurable disease, and no prior systemic treatment for locally advanced or metastatic melanoma. Previous local therapy is allowed. Previous systemic treatment for any stage III disease that was subsequently rendered NED (no evidence of disease) by surgery is allowed except for ipilimumab and BRAF inhibitors. Patients with resectable disease who do not want surgery for any reason are also allowed. Measurable disease is defined as least one lesion that can be accurately measured in two dimensions with both diameters greater than 1.0cm. For CT/MRI evaluations, an effective slice thickness is required of less than or equal to 5 mm. For slice thickness greater than 5mm, both diameters must be greater than or equal to 2.0cm at baseline.
• ECOG performance status 0, 1 or 2
• Negative pregnancy test for women of childbearing potential within 7 days of starting study treatment.
• Lab testing results in accordance with protocol WBC greater/equal to 2,000/mm3 ANC greater/equal to 1200/mm3 Platelet greater/equal 1000,000/mm2 Hemoglobin greater/equal 9 gm/dL (may be transfused) Serum bilirubin levels less/equal 1.5 mg/dL except for patients with Gilbert's syndrome.
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) less/equal 2.5 X upper limit of normal Alkaline phosphatase less/equal 2.5 times upper limit of normal Serum Creatinine levels less/equal 1.5 mg/dL Left Ventricular Ejection Fraction (LVEF) greater or equal to lower limit of normal by ECHO Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with ipilimumab or dabrafenib. Patients should agree to use an appropriate method of birth control while on study.
• Age greater than 18 years and of any gender or race. Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.