Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy
Condition: Prostate Cancer; Prostatic Neoplasms; Castrate-resistant Prostate Cancer (CRPC); Androgen-insensitive Prostate Cancer; Hormone-refractory Prostate Cancer; Metastatic Disease
MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis
Intervention: Itraconazole
Intervention description: 600 mg/day oral (PO)
IUPAC name: (2R,4S)-rel-1-(Butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one
Intervention MeSH terms: Itraconazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study evaluates if itraconazole causes a reduction in the serum levels of
      prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer
      (CRPC).
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Male aged ≥ 18 years

          -  Life expectancy ≥ 6 months

          -  Histologically- or cytologically-confirmed adenocarcinoma of the prostate

          -  Metastatic disease or prior history of metastases, as documented by positive bone scan
             or metastatic lesions on CT or MRI

          -  Prostate cancer progression, as documented by PSA according to PCWG2 or radiographic
             progression according to RECIST criteria version 1.1

          -  Progression must have been during or after docetaxel based chemotherapy.

          -  Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM).
             If the patient is currently being treated with LHRH agonists (patient who have not
             undergone an orchiectomy), this therapy must have been initiated at least 4 weeks
             prior to Cycle 1 Day 1 and treatment must be continued throughout the study.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

          -  Hemoglobin ≥ 10.0 g/dL

          -  Platelet count ≥100,000 microliters

          -  Serum creatinine ≤ 2, OR a calculated creatinine clearance ≥ 40 mL/min

          -  Serum bilirubin < 1.5 x ULN (except for patients Gilbert's disease)

          -  AST or ALT < 2.5 x ULN

          -  Able to swallow the study drug whole as a tablet

          -  Willing and able to provide written informed consent

        EXCLUSION CRITERIA

          -  Known brain metastasis

          -  Radiation therapy within 4 weeks of Cycle 1, Day 1

          -  Prior systemic treatment with an azole drug (eg, fluconazole, ketoconazole) within 4
             weeks of Cycle 1, Day 1

          -  Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose
             PSA did not decline for ≥ 3 months months in response to antiandrogen given as a 2nd
             line or later intervention will require only a 2-week washout prior to Cycle 1,Day 1)

          -  Prior Bicalutamide (Casodex), nilutamide (Nilandron) treatment within 6 weeks of Cycle
             1 Day 1 (patients whose PSA did not decline for ≥ 3 months in response to antiandrogen
             given as a 2nd line or later intervention will require only a 2-week washout prior to
             Cycle 1 Day 1)

          -  Known active or symptomatic viral hepatitis or chronic liver disease

          -  Clinically significant heart disease as evidenced by myocardial infarction or arterial
             thrombotic events in the past 6 months; severe or unstable angina

          -  Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of
             recurrence within 24 months

          -  Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1

          -  Any condition which, in the opinion of the investigator, would preclude the patient's
             participation in this trial.

          -  No more than 3 prior chemotherapy regimens.