Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer

Inclusion Criteria:

* A histologic or cytologic diagnosis of prostate cancer
* Metastatic prostate cancer with measurable and/or bony disease that has progressed despite androgen deprivation therapy and one prior chemotherapy for castrate metastatic disease; all patients must have PSA progression defined as:

  * At least 2 rises in PSA to be documented over a reference value (measure 1); the first rising PSA (measure 2) must be taken at least 7 days after the reference value; a third confirmatory PSA measure is required to be greater than the second measure and must be obtained at least 7 days after the 2nd measure; if this is not the case, a fourth PSA is required to be taken and be greater then the 2nd measure
* All patients must have a minimum PSA of \>= 5 ng/ml
* ECOG performance status of 0-2
* Testosterone \< 50 ng/dL; patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy
* No investigational or commercial agents (other than LHRH analogue) or therapies including other hormonal agents such as megestrol acetate (unless low dose given for hot flashes), antiandrogens or herbal medications may be administered with the intent to treat the patient's malignancy
* Four weeks must have elapsed since major surgery
* Prior radiotherapy is allowed as long as the bone marrow function is adequate and at least 4 weeks has elapsed since completion of radiation; no prior radiopharmaceuticals are allowed
* Life expectancy of greater than 6 months
* Ability to understand and the willingness to sign a written informed consent document that is approved by the Institutional Human Investigation Committee (HIC)
* Patients must have normal organ and marrow function as defined below obtained within two weeks from treatment initiation:
* Leukocytes \>= 3,000/mcL
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Serum creatinine \< 2 mg/DL
* Total bilirubin within normal institutional limits
* AST/ALT =\< 2.5 X institutional upper limit of normal
* Patients must be willing to provide blood samples for the correlative studies and consent to providing paraffin blocks/slides from primary prostate cancer or other prior diagnostic samples; fresh tissue sample donation is optional
* The effects of SAHA on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because HDAC inhibitors are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
* Patients with treated and controlled epidural disease are permitted into the study

Exclusion Criteria:

* Significant cardiovascular disease including congestive heart failure (New York Heart Association Class III or IV), active angina pectoris or recent myocardial infarction (within the last 6 months)
* Patients on Valproic Acid (a histone deacetylase inhibitor) must have stopped taking it at least 2 weeks prior to registration
* Oral anti-androgens must be stopped; no washout period is necessary prior to enrollment if anti-androgens were used as second line therapy and not as part of combined androgen deprivation; in the unlikely case that a patient may have continued on antiandrogen therapy as part of combined androgen deprivation and has never had antiandrogen withdrawal despite progression on combined androgen deprivation then a washout period will be needed (4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide) prior to study enrollment
* Patients who have developed progression as defined in this protocol on stable doses of oral corticosteroids are eligible; the steroids may be continued
* No "currently active" second malignancy other than non-melanoma skin cancer; patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be with no evidence of disease
* Patients with known brain metastases should be 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; however, brain scans will not be required as part of the pre-study workup
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA
* 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 with history of HIV receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SAHA; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
* Patients with the following history or clinical findings require ADDITIONAL diagnostic TESTING:

  * Patients who require diuretics for reasons other than hypertension, digoxin for reasons other than atrial fibrillation, or patients with a history of mild to moderate congestive heart failure
  * Patients with the following EKG results:

    * Significant q waves (greater than 3 mm or greater than 1/3 the height of the QRS complex
    * ST elevation or depressions of greater than 2 mm that are not attributable to hypertension strain
    * The absence of a regular sinus rhythm
    * The presence of a bundle block
  * ADDITIONAL TESTING: (if required)

    * Radionuclide angiocardiography (RNCA): Patients can be treated if the ejection fraction is \> 45% and there is no evidence of ventricular aneurysm or other abnormal wall motion; patients with an ejection fraction \< 45% on RNCA, with a worrisome but nonexclusive cardiovascular history, or an abnormal ECG as described above should also have a thallium stress test

      * STRESS TEST RESULTS:

        * Reversible defect - Exclude
        * Fixed defect alone - Include