RO4929097 in Treating Patients With Stage IV Melanoma

OBJECTIVES:

Primary

- To assess the 6-month progression-free survival and 1-year overall survival of patients
with stage IV melanoma treated with gamma-secretase inhibitor RO4929097.

Secondary

- To investigate, in a preliminary manner, the relationship between Notch activation
status and gene expression profile of tumor and clinical outcomes of patients treated
with this regimen.

- To study the effects of this regimen on T-cell function, which will provide the basis
for subsequent trials combining Notch blockade with immunomodulatory therapy for
advanced melanoma.

- To assess the response rate in patients treated with this regimen.

- To assess the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral gamma-secretase inhibitor RO4929097 on days 1-3, 8-10, and 15-17.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Some patients undergo blood collection at baseline and during study for analysis of T-cell
function by flow cytometry and ELISA. Tumor tissue samples from biopsy or surgery are also
analyzed for Notch activation by IHC and qRT-PCR.

After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for 2 years.