Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer

Inclusion Criteria:

* Histologic confirmation of adenocarcinoma of the prostate
* Biochemically relapsed disease with a rising PSA on at least two successive measurements at least two weeks apart after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy (RT) with curative intent; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to documents progression
* Prior primary or salvage radiation or not a candidate for salvage radiation due to patient preference or clinical assessment based upon disease characteristics and/or patient co-morbidities
* Minimum PSA:

  * If no prior androgen deprivation therapy (ADT) for biochemical relapse:

    * 1.0 ng/mL if prior radical prostatectomy with or without adjuvant/salvage radiation therapy, confirmed by repeat measurement at least 2 weeks later, or
    * Nadir + 2 ng/mL if prior RT alone without prior radical prostatectomy, confirmed by repeat measurement at least 2 weeks later
  * If prior ADT for biochemical relapse:

    * 4.0 ng/mL or \> 2 ng/mL above nadir on prior cycle of ADT, whichever is higher, confirmed by repeat measurement at least 2 weeks later
* No evidence of metastatic disease on imaging by whole body bone scan (technetium-99 or sodium fluoride \[Na-F\] positron emission tomography \[PET\] bone scan) and cross-sectional imaging of the abdomen/pelvis (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) within 6 weeks of day 1 of protocol therapy
* Prior androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist and/or antagonist allowed for either (neo)adjuvant treatment with local therapy or for biochemical relapse
* Last effective dose of LHRH agonist/antagonist ?expired? \> 3 months prior to study entry; for example, a patient receiving LHRH agonist injection every 3 months would be eligible provided their last injection was \> 6 months prior to day 1 of protocol therapy; a patient receiving LHRH agonist injections every 4 months will be eligible provided last injection was \> 7 months prior to day 1 of protocol therapy
* Serum testosterone level:

  * If no prior androgen deprivation therapy:

    * A single measurement greater than 150 ng/dL within 3 months of day 1 of protocol therapy
  * If prior androgen deprivation therapy (either in adjuvant or biochemical relapse setting):

    * The two most recent measurements of serum testosterone prior to day 1 of protocol therapy must fulfill the following criteria:

      * Both measurements are greater than 150 ng/dL
      * The two measurements are spaced at least 14 days apart
      * Both must be measured within 3 months of day 1 of protocol therapy
      * There must not be an increase of \> 50 ng/dL between these two successive measurements
* PSA doubling time (PSADT) =\< 15 months, calculated based upon all serum PSA measurements obtained within 3 months prior to day 1 of protocol therapy, with a minimum of three PSA measurements spaced at least 14 days apart ; PSA values obtained when serum testosterone was known to be less than 150 ng/dL, prior to local therapy, or within three months of last dose of LHRH agonist/antagonist or antiandrogen will be excluded from the calculation of the PSADT
* Total bilirubin less than 1.5 times upper limit of normal (ULN), or less than 3 times ULN at study entry in a patient with documented Gilbert?s disease
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels less than 1.5 times ULN at study entry
* Serum potassium greater than 3.5 mmol/L without oral supplementation
* No history of uncontrolled hypertension (blood pressure \> 160/100 mm Hg despite anti-hypertensive medication)
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Estimated life expectancy greater than 5 years
* Ability to sign written informed consent
* Ability to swallow study drug whole as a capsule
* Primary prostate cancer tissue available for analysis is not required for inclusion onto this study but is strongly encouraged
* Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last study drug administration

Exclusion Criteria:

* Castrate-resistant disease, as evidenced by either:

  * Rising PSA on 2 consecutive measurements at least 2 weeks apart with concurrent documented serum testosterone \< 50 ng/dL at the time of PSA measurement, or
  * Rising PSA on 2 consecutive measurements at least 2 weeks apart measured within 3 months after last LHRH agonist/antagonist injection
* Prior bilateral orchiectomy
* Congestive heart failure of New York Heart Association (NYHA) class III or higher severity at study entry
* History of chronic active hepatitis
* Grade 2 or higher peripheral neuropathy at the time of study entry
* Use of 5-alpha reductase antagonist (i.e. finasteride, dutasteride) or antiandrogen (i.e. flutamide, bicalutamide) within 6 weeks of day 1 of protocol therapy
* Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher within 6 weeks of day 1 of protocol therapy
* Use of medications or herbal supplements which are known to potentially lower serum PSA within 6 weeks of day 1 of protocol therapy
* Use of other medications that may potentially interact with itraconazole within 1 week of study entry
* Use of other investigational agents within 6 weeks of day 1 of protocol therapy
* Prior pathology consistent with small cell carcinoma or prostate cancer with predominantly neuroendocrine differentiation