Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma

Exclusion Criteria

• •Has previous systemic treatment for locally advanced or metastatic cutaneous melanoma (excluding adjuvant treatment).
• •Has non-measurable lesions, disease not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
• •Has an Eastern Cooperative Oncology Group performance status (ECOG PS) \>1.
• •Has bone marrow impairment as evidenced by Hemoglobin \<10.0 g/dL, Neutrophil count \<1.5 \* 10\^9/L, platelets \<100 \* 10\^9/L.
• •Has renal impairment as evidenced by calculated creatinine clearance \<60 mL/min (according to the Cockcroft-Gault formula).
• •Has liver function abnormality as defined by total bilirubin \>1.5 \* Upper Limit of Normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>2.5 \* ULN, for subjects with liver involvement AST/ALT \>5 \* ULN.
• •Has significant cardiac conduction abnormalities, including QTc prolongation of \>480 milliseconds and/or pacemaker or clinically relevant impaired cardiovascular function.
• •Has hypertension uncontrolled by medication
• •Has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for RVO (e.g., uncontrolled glaucoma or ocular hypertension).
• •Has known active central nervous system (CNS) metastases unless previously radiotherapy treated, stable by CT scan for at least 3 months without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants.
• •History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
• •Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B.
• •Has undergone surgical intervention within 28 days from Day 1 of trial drug treatment.
• •Has received extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from Day 1 of trial drug treatment.
• •Has history of any other significant medical disease such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion or has a psychiatric condition that might impair the subject well-being or preclude full participation in the trial.
• •Has known hypersensitivity to dacarbazine.
• •Is a pregnant or nursing female.
• •Participated in another clinical trial within the past 28 days.
• •Has creatine phosphokinase (CPK) level at baseline National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade \>=2 (i.e \> 2.5 \* ULN), and/or has a previous history of myositis or rhabdomyolysis.