A Two-dose Level Clinical Trial of Itraconazole in Patients With Metastatic Prostate Cancer Who Have Had Disease Progression While on Hormonal Therapy
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Itraconazole 200 mg; Itraconazole 300mg
Intervention description: Itraconazole, 200 mg, by mouth, once daily (200 mg total daily dose); Itraconazole, 300 mg, by mouth, twice daily (600 mg total daily dose)
Intervention MeSH terms: Itraconazole; Hydroxyitraconazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic prostate cancer; castration resistant prostate cancer; rising PSA

Summary:

      This research is being done to test an investigational drug, called itraconazole, in the
      treatment of prostate cancer. Itraconazole is approved by the Food and Drug Administration
      (FDA) for the treatment of various fungal infections such as fingernail/toenail infections
      and other more serious fungal infections. The word "investigational" means that itraconazole
      is not approved for use in people with cancer. However, the FDA is allowing the use of
      itraconazole in this research study. Itraconazole has been shown to have activity against
      cancer (including prostate cancer) in the laboratory, but has not been tested against cancer
      in humans.

      The purpose of this study is to find out:

        -  If itraconazole is safe when given at two different doses

        -  How itraconazole affects prostate specific antigen (PSA): a blood test that measures
           substances released by prostate cancer

        -  Whether itraconazole can delay further prostate cancer growth and spread

        -  How itraconazole affects other markers of prostate cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed prostate adenocarcinoma.

          -  Presence of distant metastases on bone scan, CT scan, or MRI scan.

          -  Progression after androgen deprivation (and anti-androgen withdrawal).

          -  Rising serum PSA (Prostate Cancer Working Group (PCWG2) definition).

          -  Castrate levels of serum testosterone (i.e., ≤ 50 ng/dL).

          -  Age > 18 years.

          -  ECOG performance status score ≤ 2, and/or Karnofsky score ≥ 50%.

          -  Life expectancy > 6 months.

          -  Adequate kidney, liver, and bone marrow function.

          -  Willingness to sign informed consent and adhere to study requirements.

        Exclusion Criteria:

          -  Recent surgery, radiation therapy, combined androgen blockade, or investigational
             therapies in the last 8 weeks.

          -  Previous chemotherapy for metastatic prostate cancer.

          -  Concomitant use of second-line hormonal agents (e.g., ketoconazole, DES)

          -  Current use of corticosteroids, except if on a stable dose for ≥ 3 months.

          -  History of malabsorption syndrome (may affect itraconazole absorption).

          -  Allergic reactions to itraconazole or similar compounds.

          -  Concurrent use of drugs that interact with the CYP3A4 system (caution only).

          -  Presence of known brain metastases.

          -  Prior malignancy in the last 3 years, with some exceptions.

          -  Uncontrolled major infectious, cardiac, or pulmonary illnesses.

          -  Prolonged corrected QT interval (> 450 msec) on electrocardiography.