Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer
Condition: Recurrent Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: vorinostat; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well vorinostat works in treating patients with
      progressive metastatic prostate cancer. Drugs used in chemotherapy, such as vorinostat, work
      in different ways to stop the growth of tumor cells, either by killing the cells or by
      stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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