Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer
Condition: Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage I Prostate Adenocarcinoma AJCC v7; Stage II Prostate Adenocarcinoma AJCC v7; Stage III Prostate Adenocarcinoma AJCC v7
MeSH terms: Prostatic Neoplasms; Adenocarcinoma
Intervention: Itraconazole; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Intervention MeSH terms: Itraconazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well itraconazole works in treating patients with
      biochemically relapsed prostate cancer. Itraconazole may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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