Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma

OBJECTIVES:

Primary

* To estimate the proportion of patients, with metastatic mucosal, acral, or chronically sun
damaged melanomas, whose tumors have KIT aberrations, and who progressed or could not
tolerate a KIT targeting tyrosine kinase inhibitor (TKI) (e.g. including but not limited to
imatinib mesylate, sunitinib, or dasatanib), who are alive and without progression of disease
four months after beginning treatment with nilotinib.

Secondary

- To determine early evidence of biologic and clinical activity by best overall response
rate.

- To estimate time to progression of disease and overall survival.

- To determine the tolerability of nilotinib.

- To evaluate the use of FDG-PET scanning in determining early biologic response to
therapy.

- To correlate c-kit mutational status and amplification status with response to therapy.

- To evaluate the feasibility of nilotinib.

- To evaluate the tolerability of nilotinib in patients with brain metastases.

Inclusion Criteria:

- 18 years of age or older

- Histologically documented diagnosis of mucosal melanoma or acral melanoma or
chronically sun damaged melanoma as evidenced by solar elastosis on pathology

- Patient's tumor with evidence for KIT mutation or amplification. Patient tumors that
already have documented mutations or amplification do not have to have tissue
submitted again for analysis to confirm eligibility

- Have failed, progressed, or not been able to tolerate other tyrosine kinase inhibitors
including but not limited to imatinib mesylate, sunitinib or dasatinib treatment.

- At least one measurable site of disease

- ECOG Performance Status 0, 1 or 2

- Adequate organ function as outlined in the protocol

- Negative pregnancy test for female patients of childbearing potential

Exclusion Criteria:

- Patient has received any other investigational agents within 28 days of first day of
study drug dosing unless the disease is rapidly progressing

- Patient is < 5 years free of another primary malignancy except: if the other primary
malignancy is not currently clinically significant nor requiring active intervention,
or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
situ

- Female patients who are pregnant or breast-feeding

- Patient has a severe and/or uncontrolled medical disease

- Patient has a rare hereditary problem of galactose intolerance, severe lactase
deficiency or of glucose-galactose malabsorption

- Patient with electrolyte abnormality unless the level can be corrected to normal
levels prior to initiating study drug

- Known brain metastasis

- Known chronic liver disease

- Patient has received chemotherapy within 4 weeks prior to study entry, unless the
disease is rapidly progressing (6 weeks for nitrosourea or mitomycin-C)

- Patient previously received radiotherapy to 25% or greater of the bone marrow

- Patient had a major surgery within 2 weeks prior to study entry

- Impaired cardiac function

- QTc > 450msec on screening ECG

- Myocardial infarction within one year prior to starting nilotinib

- Other clinically significant heart disease

- Patients who are currently receiving treatment with any of the medications that have
the potential to prolong QT interval

- Patients who are currently receiving Warfarin > 1mg/day

- Patient with any significant history of non-compliance to medical regimens or with the
inability to grant reliable informed consent

- Prior therapy with nilotinib