Vemurafenib and Recombinant Interferon alfa-2b in Treating Patients With Stage III-IV Melanoma

Inclusion Criteria

• Patients must have a written informed consent obtained prior to the initiation of study procedures
• Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification); cutaneous melanoma, ocular or mucosal melanoma will be eligible
• Only patients with v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutated tumors will be enrolled
• Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised; adequate wound healing is required prior to study entry; baseline skin exam is required for all patients
• Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); baseline measurements must be obtained within 4 weeks prior to initiating therapy; at least 1 of the tumor sites must be amenable to surgical or core biopsy
• White blood cell (WBC) >= 3,000/mm^3
• Absolute neutrophil count (ANC) >= 1500
• Hemoglobin (Hb) >= 9g/dL (women) or >= 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
• Platelets >= 100,000/mm^3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
• Serum creatinine =< 1.5 x upper limit of normal (ULN)
• Serum bilirubin =< 1.5 x ULN
• Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Patients must have an electrocardiogram (EKG) documenting normal intervals (especially QTc interval < 480 msec) and no arrhythmia prior to enrollment
• Patients must have fully recovered from any effects of major surgery, and be free of significant detectable infection
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must be free of active brain metastases by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans within 4 weeks prior to starting the study drugs; if known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on two successive MRI evaluations at least 3 months apart (one of which is at least 4 weeks prior to starting the study drugs)
• Female patients of child bearing potential must have a negative pregnancy test (within 7 days from the time of randomization); patients must agree to use effective contraception (both males and females) for 2 weeks prior to the first dose of each study treatment and for 8 weeks after the last dose of each study treatment

Exclusion Criteria

• Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders; this includes known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness, or active hepatitis B virus (HBV) and hepatitis C virus (HCV)
• Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or mitogen-activated protein kinase kinase (MEK) and/or extracellular signal-regulated kinase (ERK) inhibitors
• Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption
• Mean QTc interval >= 480 msec at screening
• Recent acute coronary syndrome (ACS)/acute myocardial infarction (AMI) – defined as within 24 weeks prior to screening
• Recent percutaneous coronary intervention (PCI)/percutaneous transluminal coronary angioplasty (PTCA) – defined as within 24 weeks prior to screening
• Recent malignant cardiac arrhythmias – all except sinus arrhythmia within 24 weeks prior to screening
• Symptomatic heart failure – New York Heart Association (NYHA) class >= II symptoms
• Active infection or antibiotics within one-week prior to study, including unexplained fever; any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial
• Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study
• Lactating females or pregnant females