A Phase II Study of Lapatinib for the Treatment of Stage IV Melanoma Harboring ERBB4 Mutations

Background:

• Studies of melanoma tumor samples have shown that tumor cells from approximately 20 percent of melanoma patients contain a specific mutation of a gene involved in making a protein called ERBB4, and that changes in this gene have been associated with cancer. Lapatinib, a drug that is currently approved for the treatment of breast cancer, has been shown in the laboratory to significantly slow the growth of melanoma cells that contain this specific ERBB4 gene mutation. Researchers are interested in determining whether lapatinib can be effective against melanoma in individuals who have the ERBB4 mutation.

Objectives:

• To evaluate the safety and effectiveness of lapatinib as a treatment for melanoma with ERBB4 mutation that has not responded to standard therapy.

Eligibility:

• Individuals at least 18 years of age who have stage 4 melanoma that has not responded to standard therapy.

Design:

• Participants will be screened with a full physical examination and medical history, as well as tests of tumor tissue taken from previous surgeries or biopsies or from a new biopsy that will be conducted before the start of the study. Test results to determine eligibility will be available within about 2 weeks.
• Participants will take four lapatinib tablets daily (two in the morning, 1 hour before or after breakfast and two in the evening, 1 hour before or after dinner) during every 28-day cycle of treatment. Participants will keep a medication diary to record tablets taken and any side effects from the medication.
• After the first 2 weeks, and every 2 to 4 weeks afterward for the first 12 weeks, participants will have clinic visits with blood samples and other tests to determine if lapatinib is causing their disease to shrink or be controlled. If the disease has not progressed, participants will continue to receive a new lapatinib supply every 28 days for up to 2 years (27 cycles), and will continue to have regular clinic visits to monitor the progress of treatment.
• When tumor tissue is easily accessible and can be easily biopsied, researchers will collect two additional biopsies, one after 2 weeks of treatment and one after 12 weeks of treatment....