Hsp90 Inhibitor STA-9090 in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy

PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) achieved with STA-9090 (Hsp90 inhibitor
STA-9090) in men with castration-resistant prostate cancer (CRPC) who have received prior
docetaxel based therapy.

SECONDARY OBJECTIVES:

I. To assess the percentage change in prostate-specific antigen (PSA) from baseline to 12
weeks.

II. To assess overall safety and tolerability of STA-9090. III. To evaluate overall survival
(OS) outcome in metastatic CRPC who have received prior docetaxel therapy.

IV. To investigate the association of progression-free survival (PFS) and PSA response rate
with primary and secondary target markers.

TERTIARY OBJECTIVES:

I. To evaluate potential markers for predicting drug response or efficacy, blood samples will
be used to collect the serum and extract messenger ribonucleic acid (mRNA) from mononuclear
cells and analyzed by quantitative real-time polymerase chain reaction (PCR) and/or
enzyme-linked immunosorbent assay (ELISA).

OUTLINE:

Patients receive Hsp90 inhibitor STA-9090 intravenously (IV) over 1 hour once weekly in weeks
1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 4 weeks.

Inclusion Criteria:

- Pathologically confirmed diagnosis of prostate adenocarcinoma with metastasis and
objective progression or rising PSA despite androgen deprivation therapy and
antiandrogen withdrawal when applicable

- Progression after docetaxel based chemotherapy is needed as follows:

- a) If measurable disease present, then either rising PSA, increase in size of the
lesion/s or both should be present

- b) Patients with rising PSA only as progression must demonstrate a rising trend with 2
successive elevations at minimum intervals of 1 week; a minimum PSA of 5 ng/ml, or new
areas of bony metastases on bone scan are required for patients with no measurable
disease; no minimum PSA requirement for patients with measurable disease

- Patients should have received at least one prior docetaxel based regimen for
metastatic disease; no maximum prior therapy

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2

- Life expectancy of at least 3 months

- Prior radiation therapy or chemotherapy completed at least 28 days prior to enrollment

- All patients must be documented to be castrate with a testosterone level =< 0.5 ng/ml;
luteinizing-hormone-releasing hormone (LHRH) agonist therapy must be continued, if
required to maintain castrate levels of testosterone; patients must be off
antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or
nilutamide

- Absolute neutrophil count >= 1,500 cells/uL

- Platelets >= 100,000/uL

- Hemoglobin >= 9.0 g/dL

- Serum creatinine =< 1.5 x upper limit of normal (ULN); Note: if serum creatinine is >
1.5 x ULN, subject is eligible if the calculated creatinine clearance (CLcr) is >= 50
mL/min

- Total bilirubin =< 1.5 x ULN

- For patients without documented bone metastases or for patients with liver metastases:
transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic
transaminase [SGOT] and/or alanine aminotransferase (ALT)/serum glutamic pyruvic
transaminase [SGPT]) may be up to 2.5 x institutional ULN if alkaline phosphatase is
=< ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are =< ULN

- For patients with documented bone metastases, the transaminases (AST/SGOT and/or
ALT/SGPT) should be less than 2.5 x institutional ULN, without regard to the alkaline
phosphatase level

- Sexually active males must use measures to prevent pregnancy in their partners while
on STA-9090

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other study procedures

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

Exclusion Criteria:

- Major surgery within 4 weeks prior to first dose of STA-9090

- Poor venous access for study drug administration or would require a peripheral or
central indwelling catheter for study drug administration; study drug administration
via indwelling catheters is prohibited at this time

- Use of any chemotherapy or other standard systemic treatments for prostate cancer,
including investigational agents within 2 weeks or 6 half- lives of the agent,
whichever is shorter, prior to receiving STA-9090; there must be at least 2 weeks
between the end of palliative radiation and the start of study drug and all radiation
therapy (XRT)-associated toxicities resolved to Grade 1 or 0

- History of severe allergic or hypersensitivity reactions to excipients (e.g.,
Polyethylene glycol [PEG] 300 and Polysorbate 80 [i.e. docetaxel])

- Baseline QTc > 450 msec or previous history of QT prolongation while taking other
medications

- Ventricular ejection fraction (Ef) =< 55% at baseline

- Any history of current coronary artery disease, myocardial infarction, angina
pectoris, angioplasty or coronary bypass surgery

- History of current uncontrolled dysrhythmias, or requirement for antiarrhythmic
medications, or Grade 2 or greater left bundle branch block

- New York Heart Association class II/III/IV congestive heart failure with a history of
dyspnea, orthopnea, or edema that requires current treatment with angiotensin
converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or
diuretics

- Current or prior radiation therapy to the left hemithorax

- Treatment with chronic immunosuppressants (e.g. cyclosporine following
transplantation)

- Uncontrolled intercurrent illness including, but not limited to, human
immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral
therapy, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements

- Other medications, or severe acute/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 would make the subject inappropriate
for entry into this study