Ketoconazole and Dexamethasone in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Ketoconazole; Hydrocortisone; Dexamethasone
Intervention description: 200mg during first week of study (run-in phase), then 400mg po tid; Hydrocortisone 20mg po qam and 10mg po qpm
If participant has ≥30% PSA decline at 12 week evaluation, treatment continues until progressive disease (by RECIST criteria OR by PSAWG criteria) is documented. After that, drug will be discontinued. If participant has <30% PSA decline, patient goes off study.; Dexamethasone 0.5mg po bid
If ≥ 30% PSA decline (Prostate-specific antigen) at 12 week evaluation, administration starts when disease progression (by RECIST criteria OR by PSAWG criteria) is documented.
Intervention MeSH terms: Ketoconazole; Dexamethasone; Dexamethasone acetate; Hydrocortisone; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ketoconazole; Dexamethasone

Summary:

      This is an open label, phase II, single center trial of ketoconazole/dexamethasone to
      determine if the administration of ketoconazole/dexamethasone, after disease progression with
      ketoconazole/hydrocortisone slows or reverses disease progression in men with progressive
      prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate.

          -  Testosterone < 50 ng/dL. Participants must continue primary androgen deprivation with
             an luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone
             orchiectomy.

          -  Progressive non-metastatic or metastatic disease after androgen deprivation.
             Participants must have EITHER:

               1. Progression as defined by RECIST criteria. OR

               2. Progressive PSA documented within 4 weeks of enrollment. PSA evidence for
                  progressive prostate cancer consists of a PSA level of at least 5 ng/ml which has
                  risen on at least 2 successive occasions, at least 2 weeks apart. If the
                  confirmatory PSA value is less than the first documented rising PSA value, then
                  an additional test for rising PSA will be required to document progression.

          -  Participants who are receiving an antiandrogen as part of primary androgen ablation
             must demonstrate disease progression following discontinuation of antiandrogen.

               1. Disease progression after antiandrogen withdrawal is defined as 2 consecutive
                  rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft
                  tissue progression.

               2. For participants receiving flutamide, at least one of the PSA values must be
                  obtained 4 weeks or more after flutamide discontinuation.

               3. For participants receiving bicalutamide (Casodex) or nilutamide, at least one of
                  the PSA values must be obtained 6 weeks or more after antiandrogen
                  discontinuation.

          -  Karnofsky Performance Status ≥ 60%.

          -  Participants receiving any other hormonal therapy, including any dose of megestrol
             acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA
             levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must
             discontinue the agent for at least 4 weeks prior to enrollment.

          -  Participants on stable doses of bisphosphonates may continue on this medication;
             further, patients may initiate bisphosphonate therapy at the time of ketoconazole
             initiation.

          -  Prior radiation therapy completed ≥ 4 weeks prior to enrollment.

          -  Liver function tests (alanine aminotransferase (ALT), aspartate aminotransferase
             (AST), and Bilirubin) must be within normal limits.

          -  Absolute Neutrophil Count (ANC) >1500/µl, Platelet count > 100,00/µl, Creatinine <1.5
             x upper limit of normal (ULN), Hemoglobin > 8 mg/dl.

        Exclusion Criteria:

          -  Prior chemotherapy for prostate cancer is not allowed with the exception of cases in
             which chemotherapy has been administered in a neoadjuvant or adjuvant fashion AND >1
             year has elapsed since the administration of this therapy.

          -  No prior ketoconazole, abiraterone, aminoglutethimide or corticosteroids for treatment
             of progressive prostate cancer.

          -  No supplements or complementary medicines/botanicals are permitted while on protocol
             therapy, except for any combination of the following: (conventional multivitamin
             supplements, selenium, lycopene, soy supplements) No prior radiopharmaceuticals
             (strontium, samarium) within 8 weeks prior to enrollment.

          -  No "currently active" second malignancy, other than non-melanoma skin cancer.

          -  No serious intercurrent infections or nonmalignant medical illnesses that are
             uncontrolled.

          -  No psychiatric illnesses/social situations that would limit compliance

          -  No active or uncontrolled autoimmune disease.

          -  No adrenal insufficiency as demonstrated by a baseline adrenocorticotropic hormone
             (ACTH) stimulation test demonstrating a peak cortisol >18 µg/dL.