Lapatinib in Stage IV Melanoma With ERBB4 Mutations

Background: * Patients with stage IV melanoma have few available treatment options and an overall poor prognosis. * Pre-clinical evidence suggests that lapatinib has activity against metastatic melanoma harboring ERBB4 mutations. Objectives: Primary Objectives: -Determine the response rate to lapatinib administered as 500 mg orally twice daily on a continuous schedule in patients with metastatic melanoma harboring ERBB4 mutations. Secondary Objectives: * To determine the progression free survival of patients with stage IV melanoma treated with lapatinib monotherapy. * To evaluate the safety of lapatinib in patients with metastatic melanoma * To determine the impact of additional genetic alterations on the response to lapatinib in melanoma harboring ERBB4 mutations * To develop a clinically applicable biomarker predictive of response to lapatinib in patients with melanoma harboring ERBB4 mutations * To determine the pharmacokinetics of lapatinib administered as 500 mg orally twice daily on a continuous schedule in patients with metastatic melanoma harboring ERBB4 mutations Eligibility: * Patients greater than or equal to 18 years of age with stage IV melanoma, who have measurable disease and whose tumors express up to two ERBB4 gene mutations. * Patient must be Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1 and a life expectancy of more than 3 months. * Patients must have adequate organ function. * Patients must not have had surgery, chemotherapy, hormonal therapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study medication. * Patients must not have an acute, critical illness. * All patients who are sexually active and able to conceive will be required to use contraception during treatment with lapatinib. Design: * Patients will be screened for the presence of ERBB4 gene mutations in their tumor and only patients who harbor less than or equal to 2 ERBB4 mutations will be enrolled in the treatment phase of the study. * Lapatinib will be administered as an oral dose of 500 mg twice daily (in the morning and evening) taken one hour before or after meals. Lapatinib will be given continuously; one cycle equals 28 days. Course 1 equals cycle 1; all subsequent courses are 8 weeks long (2 cycles). A patient may receive up to 27 cycles (14 courses). * Up to 25 patients (allowing for a staged accrual of initially 16 patients who will receive lapatinib and are evaluable after the 1st cycle) will be enrolled over 2-3 years and the trial will be completed over 3-5 years, allowing for completion of follow-up. * The primary objective of the trial will be to determine whether lapatinib monotherapy in this setting is able to be associated with a response rate (Partial Response (PR) + Complete Response (CR)) that can rule out 10% (p0=0.10) in favor of an improved response rate of 30% (p1=0.30).