To determine:

• Anti-tumor activity of IPI-504 in 2 groups of subjects with hormone resistant prostate cancer.
• Group A - subjects who have not previously received chemotherapy
• Group B - sujects who have received prior chemotherapy or could not tolerate chemotherapy.
• Clinical response will be determined by PSA and radiological response

IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. Inhibition of HSP-90 leads to the proteasomal degradation of these proteins.

In patients with HRPC,there are several proteins that are important in the progression of HRPC, including AR, AKT and Her-2. All of these are client proteins of Hsp90 and in response to Hsp90 inhibition are degraded by their proteasome. Preclinical studies have shown that Hsp90 inhibition causes a dose dependent degradation of these client proteins and growth inhibition of prostate cancer in xenograft tumors.

Inclusion Criteria:

• Adenocarcinoma of the prostate

• Resolution of acute toxic side effects of prior chemotherapy

• Castration resistant disease despite ongoing chemical or surgical castration

• ECOG 0-1

• PSA greater than or equal to 2

• Group A -

  • No Prior treatment for prostate cancer with cytotoxic chemotherapy (neoadjuvant, adjuvant treatment permitted if more than 2 years out)

• Group B

  • Radiographic evidence of metastatic disease
  • Prior tx with docetaxel-minimum of 2 cycles with progression by RECIST or PSA or intolerant of tx
  • Maximum of 3 prior chemotherapies

Exclusion Criteria:

• Small cell carcinoma of the prostate
• Treatment within 2 weeks with approved, investigational, or small molecule
• Treatment within 4 weeks with biologic or external beam radiation
• ANC <1,500 cells m3; Platelets <100,000 mm3; Hemoglobin <9.0g/dL
• AST/ALT >2.5 ULN
• Serum creatinine >3.0mg/dL
• Active keratitis or keratoconjunctivitis
• Previous treatment with 17-AAG, DMAG; or any other HSP-90 inhibitor
• Baseline Qtc >450 mses