Study of ATN-224 in Patients With Prostate Cancer

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