Inclusion Criteria

Inclusion Criteria

- Patients with histologically confirmed, advanced cutaneous melanoma. Advanced
melanoma is defined as locally advanced disease that is not amenable to surgery or
radiation therapy and metastatic disease. Patients may have had adjuvant treatment
for prior early disease as long as it was given at least 6 months before the first
dose of study medication, and the treatment did not contain temozolomide or
dacarbazine. Previous treatment for advanced disease is acceptable as long as the
patient did not receive temozolomide or dacarbazine. There is no restriction on the
number of prior regimens.

- Age ≥18 years

- Life expectancy of greater than 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥50%; see
Appendix A)

- Patients must have adequate organ and marrow function as defined below:

- absolute neutrophil count ≥1,500/uL

- platelets ≥100,000/uL

- hemoglobin ≥9 g/dL

- total bilirubin ≤2 X institutional upper limit of normal (ULN)

- AST(SGOT) and ALT(SGPT) ≤2 X ULN

- creatinine clearance (measured or calculated) ≥30 mL/min

Patients are allowed to receive erythropoietin or blood transfusions before receiving
their first dose of ATN-224 to bring the hemoglobin level to >9 g/dL to meet eligibility
criteria.

- Use of adequate contraception. Temozolomide has the potential to cause fetal harm.
The effects of ATN 224 on the developing human fetus at the recommended therapeutic
dose are unknown, but antiangiogenic agents are known to be teratogenic. For these
reasons women of child-bearing potential and men with partners of child-bearing
potential must agree to use adequate contraception (hormonal and/or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation through the follow up visit 28 days after the last dose of ATN 224 or
temozolomide.

- Willingness to forgo taking copper- or zinc-containing vitamins or supplements

- Ability to understand and the willingness to sign a written informed consent document

- Uveal (ocular) melanoma

- Brain metastasis that has not been treated and remained stable for at least 4 weeks
(In other words, patients are eligible if they have no metastases or if brain
metastases have been treated and remain stable for at least 4 weeks)

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ATN-224 or omeprazole

- History of malabsorption syndromes or other gastrointestinal disorders that may
affect ATN-224 or temozolomide absorption, including bowel obstruction, celiac
disease, sprue, cystic fibrosis

- Ineligible to receive either temozolomide (Temodar®), omeprazole (Prilosec®),
lansoprazole (Prevacid®), pantoprazole (Protonix®), or ranitidine (Zantac®)

- Inability to swallow study medication capsules

- Other serious medical or psychiatric illness preventing informed consent or with the
potential to interfere with assessment of safety or efficacy of ATN-224 treatment

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Patients known to be positive for HIV or infectious hepatitis type A, B or C

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease-free for 5 years