A Randomized, Phase II Study of Two Dose Levels of ATN-224 in Patients With Biochemically Relapsed, Early Stage Prostate Cancer Not on Hormone Therapy

Inclusion Criteria

Inclusion Criteria

- Patients with histologically confirmed, localized prostate cancer who have a
prostate-specific antigen (PSA) doubling time (DT) as calculated according to the
Memorial Sloan-Kettering Cancer Center nomogram
(http://www.mskcc.org/mskcc/html/10088.cfm)

- Doubling time < 12 months after local therapy in patients who have not had any
previous hormone therapy, or

- Doubling time < 12 months starting at least 6 months after their last dose of
hormone therapy

- Patients must have a serum testosterone >150 ng/dL at the time of study entry.
Patients may have received previous castrating hormonal therapy or anti-androgens,
provided that the testosterone level is >150 ng/dL at the time of study entry. Prior
chemotherapy is also allowed as long as the requirements for adequate organ and
marrow function are met.

- No detectable disease as assessed by physical examination and bone and CT (abdomen
and pelvis) scans within 4 weeks prior to the first dose of ATN-224

- A minimum of three PSA values, each at least 4 weeks apart, to calculate PSA-DT. The
last PSA level prior to enrollment must be at least 2.0 ng/mL and be rising over the
prior value.

- 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

- serum testosterone >150 ng/mL or return to pre-treatment values for patients who
received hormone therapy

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.

- At least 28 days from receiving any investigational agent

- The effects of ATN-224 on sperm at the recommended therapeutic dose are unknown. For
this reason 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

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

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

Exclusion Criteria

- Patients who have had radiotherapy within 3 months prior to the first dose of ATN 224

- 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 or other long acting antacids

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

- Ineligible to receive either 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 or any other cancer from which the patient
has been disease-free for 5 years

- Patients receiving steroid therapy for concurrent illness unless they have been on a
stable dose for 3 months.

- Patients receiving hormonal therapy including gonadotropin-releasing hormone
agonist/antagonist, antiandrogens, diethylstilbestrol, any other estrogen-like
agents, any hormonally active over-the-counter compounds such as PC-SPES or
finasteride