A Phase II Study of Satraplatin and Prednisone in Metastatic Androgen Independent Prostate Cancer (AIPC)

Inclusion Criteria

- INCLUSION CRITERIA:

A. Patients must have histopathological confirmation of prostate cancer by the Laboratory
of Pathology of the National Cancer Institute (NCI) or Pathology Department of the
National Naval Medical Center or Walter Reed Army Medical Center prior to entering this
study. Patients whose pathology specimens are not available may be enrolled in the trial
if the patient has a clinical course consistent with prostate cancer and available
documentation from an outside pathology laboratory of the diagnosis. In cases where
original tissue blocks or archival biopsy material is available, all efforts should be
made to have the material forwarded to the research team for use in correlative studies.

B. Patients must have metastatic progressive androgen-independent prostate cancer. There
must be radiographic evidence of disease (by computed tomography (CT) scan or bone scan)
after primary treatment that has continued to progress despite hormonal agents.
Progression requires that a measurable lesion is expanding, new lesions have appeared,
and/or that prostatic specific antigen (PSA) is continuing to rise on successive
measurements. Patients must have progressive disease after receiving 1 prior
docetaxel-based cytotoxic chemotherapy. Patients on flutamide for the prior 6 months must
have disease progression at least 4 weeks after withdrawal. Patients on bicalutamide or
nilutamide must have progression at least 6 weeks after withdrawal.

C. Patients may only have received 1 prior cytotoxic chemotherapy. For the purpose of
this study, multiple courses of a taxane-based regimen may count as a single regimen.
Multiple courses of a non-taxane agent or a combination chemotherapy regimen, administered
in a similar fashion may count as a single regimen.

D. Patients must have a life expectancy of more than 3 months.

E. Patients must have a performance status of 0 to 2 according to the Eastern Cooperative
Oncology Group (ECOG) criteria.

F. Patients must have adequate organ function as defined below:

Leukocytes greater than or equal to 3,000/microl.

Absolute Neutrophil Count greater than or equal to 1,500/microl.

Platelets greater than or equal to 100,000/microl.

Total bilirubin less than or equal to 1.5 times institutional upper limits of normal
(Except patients with Gilbert's disease who may proceed despite elevated total bilirubin).

Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase(SGOT) and alanine
aminotransferase (ALT)serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5
times institutional upper limit of normal

Creatinine less than or equal to 1.5 times institutional upper limits of normal.

OR

Creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal.

G. Patients must have recovered from any acute toxicity related to prior therapy,
including surgery. Toxicity should be <= grade 1 or returned to baseline.

H. Hormonal profile: all patients who have not undergone bilateral surgical castration
must continue suppression of testosterone production by appropriate usage of gonadotropin
releasing hormone (GnRH) agonists.

I. Patients must not have any ongoing malignancies requiring active therapy.

J. Patients must be able to understand and sign an informed consent form.

K. Concurrent use of bisphosphonates will be allowed if patients have previously been on
it; if patients are not on bisphosphonates at the time of study enrollment,
bisphosphonates may be started at cycle 2.

L. Patients who require hematopoietic growth factor support (e.g. epogen, darbepoetin),
but not myeloid growth factors (except after cycle 1 day 1 if clinically indicated),
non-steroidal anti-inflammatory drug (NSAIDs), and other maintenance medications prior to
study entry will be allowed to continue their supportive therapies.

M. Results from embryo-fetal development indicated that satraplatin should be considered a
teratogen in women of childbearing potential and hazardous in respect to spermatogenesis
for men. For this reason, men must agree to use adequate contraception (abstinence;
hormonal or barrier method of birth control) prior to study entry and for the duration of
study participation.

N. Patients must be able to swallow capsules.

O. Patients on chronic stable steroids (equivalent to no more than 10 mg of prednisone
daily dose) used for non-cancer treatment may be allowed on study.

EXCLUSION CRITERIA:

A. Patients who have had prior treatment with satraplatin or other platinum containing
compounds will be excluded.

B. Patients may not be receiving any other investigational agents.

C. Patients with known active brain metastases are excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events.

D. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to satraplatin or prednisone.

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

F. Prior radiation therapy to greater than 30 percent of the bone marrow, or who have
received strontium-89, rhenium-186, or rhenium-188 will be excluded from this trial.
Patients who have received prior radiotherapy must have recovered from acute toxicity due
to radiation. Patients who have received samarium-153 are eligible for the study because
samarium has a significantly reduced half-life compared to aforementioned isotopes.

G. Patients with immune deficiency are at increased risk of lethal infections when treated
with marrow-suppressive therapy. Therefore, human immunodeficiency virus (HIV)-positive
patients are excluded from the study.

H. Patients with a history of major gastrointestinal surgery or pathology likely to
influence absorption of oral medications, like bypass surgeries, Whipple's procedure, or
any surgery that would impair reliable absorption of oral drugs.

I. Patients with a disease where corticosteroids are contraindicated, e.g. active gastric
or duodenal ulcer, or poorly controlled insulin dependent diabetes. Patients with
well-controlled insulin-dependent diabetes mellitus may be considered, providing they
understand their glucose levels will increase, and their insulin dose will require
adjusting.

J. Because no dosing or adverse event data are currently available on the use of
satraplatin in patients less than 18 years of age, children are excluded from this study.