SB939 in Treating Patients With Recurrent or Metastatic Prostate Cancer

This is an interventional treatment trial for Prostate Cancer focused on measuring hormone-resistant prostate cancer, recurrent prostate cancer, stage IV prostate cancer, stage III prostate cancer, adenocarcinoma of the prostate Read More

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Presence of clinically and/or radiologically documented disease (target or non-target)

• Metastatic or locally recurrent disease for which no curative therapy exists AND for which systemic chemotherapy is indicated due to progression, meeting the following criteria:

  • At least two rises in PSA over a reference value OR the development of new metastatic lesions with a stable or rising PSA

    • First rising PSA must be taken at least 1 week after the reference value
    • Third or subsequent PSA must show further increase confirming progression within 2 weeks prior to study enrollment
    • PSA progression must be documented after discontinuation of peripheral antiandrogens (4 weeks for flutamide and 6 weeks for bicalutamide/nilutamide) for patients with documented evidence of progression while receiving peripheral antiandrogens

• Medically or surgically castrated by androgen ablation

  • Castrate level of testosterone (< 1.7 nmol/L) must be present for patients undergoing medical androgen ablation

• Received prior hormone therapy

  • Must have hormone-refractory disease
  • Therapy with luteinizing hormone-releasing hormone (LHRH) agonist must continue for patients already receiving this treatment at the time of enrollment
  • Patients who discontinued LHRH agonist must restart therapy (if not surgically castrated) and the castrate level of testosterone must be present
• PSA ≥ 5 ng/mL
• Primary or metastatic tumor tissue available
• No documented CNS metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Absolute granulocyte count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin normal
• Serum creatinine normal
• Potassium normal
• Calcium normal
• Fertile patients must use effective contraception
• QTc ≤ 450 msec
• LVEF ≥ 50% by Echo or MUGA scan
• Troponin I or T ≤ ULN
• Able to take oral medication
• No preexisting uncontrolled cardiac condition
• No prior myocardial infarction
• No history of other malignancies, except adequately treated nonmelanoma skin cancer or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• No gastrointestinal abnormalities (e.g., bowel obstruction or previous gastric resection) that would lead to inadequate absorption of HDAC Inhibitor SB939
• No known HIV positivity or hepatitis B or C infections

• No chronic medical condition or comorbidity that may increase the risks associated with study participation/study drug administration or may interfere with the interpretation of study results, including any of the following:

  • Pulmonary disease
  • Active infection
  • Psychiatric condition
  • Laboratory abnormality

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior antiandrogens (6 weeks for bicalutamide)

• At least 4 weeks since prior external-beam radiotherapy

  • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
• At least 28 days since other prior investigational therapy or anticancer therapy
• At least 14 days since prior major surgery and wound healing has occurred
• No more than 1 prior chemotherapy regimen allowed and recovered from significant toxicity
• No prior strontium
• No prior HDAC inhibitors
• No current agents (dysrhythmic drugs) with a known risk of Torsades de Pointes
• No other concurrent cytotoxic therapy or radiotherapy
• No other concurrent investigational therapy