A Safety and Feasibility Study of Mitotane in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Mitotane
Intervention description: Mitotane will be administered at a starting dose of 1.5 g/day and increased in case of good gastrointestinal tolerance every 3rd day by 0.5 g up to a maximal dose of 5.0 g and then adjusted according to blood concentrations monthly and tolerability, up to a maximum of 10g daily
Intervention MeSH terms: Mitotane
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      1. The primary objective of this study is to assess the feasibility of treating patients
           with metastatic castration resistant prostate cancer with mitotane. Secondary objectives
           are to assess safety and tolerability as well as response rate of therapy

        2. To assess the toxicity of Mitotane in men with HRPC

        3. To assess the relationship between baseline serum adrenal androgens and their response
           to Mitotane
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biopsy-proven prostate cancer OR a clinical picture consistent with metastatic
             prostate cancer with high levels of serum PSA (>20ng/ml)

          -  Progressed on docetaxel chemotherapy after a minimum of 3 cycles and/or stopped
             treatment because of toxicity. Patients may have had previous mitoxantrone, either
             before or after docetaxel treatment

          -  Response to a minimum of a 50% fall in PSA maintained for 4 weeks and then progressed
             through abiraterone treatment

          -  At least 2 consecutive rising PSAs measured at least 1 week apart . Patients must have
             ceased abiraterone at least 1 week prior.

          -  Serum PSA > 10 ng/ml

          -  ECOG performance status </= 1 (Karnofsky >/=60%)

          -  Normal organ and marrow function as defined:

               -  Absolute neutrophils count ≥ 1,500/uL

               -  platelets ≥100,000/uL

               -  total bilirubin ≤1.5 X institutional ULN

               -  AST(SGOT)/ALT(SGPT) ≤ 2 X institutional ULN

               -  creatinine ≤ 1.5 X institutional ULN

          -  Men must agree to use adequate contraception prior to study entry

          -  Life expectancy > 3 months

          -  CRPC documented by PSA increase despite having: a) orchidectomy OR b) continuous LHRH
             agonist treatment. This should be documented by a baseline serum testosterone
             suppression (<1.75 nmol/L)

        Exclusion Criteria:

          -  Prior anticancer treatment with Mitotane

          -  May not be receiving any other investigational or anticancer agents while on study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure or evidence of cardiac dysfunction,
             unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, poorly
             controlled diabetes mellitus, clinically significant or untreated ophthalmologic (e.g.
             Sjogrens etc.) or gastrointestinal conditions (e.g. Crohns disease, ulcerative
             colitis) or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Active malignancy at any other site excluding squamous cell or basal cell carcinomas
             of the skin

          -  Radiotherapy within the past 4 weeks

          -  Pre-existing pituitary or adrenal dysfunction

          -  Patients on spironolactone as this may interfere with the action of mitotane

          -  Patients on warfarin as mitotane may unpredictably interfere with INR measurements