A Phase I/II Dose Escalating Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of TKI258 (CHIR-258) in Patients With Locally Advanced or Metastatic Melanoma

Inclusion Criteria:

- Confirmed diagnosis of locally advanced or metastatic melanoma (American Joint
Committee on Cancer [AJCC] stage IIIB, IIIC or IV) that is refractory to standard
therapy or for which no curative standard therapy exists.

- Measurable disease

- Must be eighteen years of age or older

- Must meet baseline laboratory requirements

- ECOG performance status 0 or 1

- Adults of reproductive potential must agree to use effective contraception or be
sterile

Exclusion Criteria:

- Concurrent therapy with any other investigational agent

- Uncontrolled central nervous system metastases

- Impaired cardiac function or clinically significant cardiac disease

- Received

- chemotherapy, targeted therapy or monoclonal antibody therapy ≤4 weeks

- biological therapy or immunotherapy (therapeutic or diagnostic) ≤2 weeks

- an investigational agent (therapeutic or diagnostic) ≤4 weeks prior to starting
study drug or has not recovered from side effects of such therapy

- Received any hematopoietic colony-stimulating factor (e.g., G-CSF, GM-CSF) ≤ 2 weeks
prior to starting study drug. Erythropoietin is allowed.

- Has undergone major surgery ≤ 2 weeks prior to starting study drug or has not
recovered from side effects of such surgery.

- Malabsorption syndrome or uncontrolled gastrointestinal symptoms such as nausea,
diarrhea, vomiting

- Pregnant or breast feeding women

- History of another primary malignancy that is currently clinically significant or
currently requires active intervention.

- Chronic anticoagulation therapy with full strength aspirin, Coumadin, or heparin.

- History of thromboembolic or cerebrovascular events within the last 12 months.

- History of rectal bleeding, bloody vomit, or spitting up blood within the last 3
months.

- Known diagnosis of HIV infection (HIV testing is not mandatory)

- Use of ketoconazole, erythromycin, carbamazepine, phenobarbital, phenytoin, rifampin,
St. John's wort and quinidine is prohibited.

- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
study-drug administration or may interfere with the interpretation of study results
and, in the judgment of the investigator, make the patient inappropriate for this
study