Enzalutamide for Bladder Cancer Chemoprevention
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Enzalutamide
Intervention description: 160 mg by mouth daily for 12 months
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Enzalutamide; Non-Muscle Invasive Bladder Cancer; Androgen Deprivation Therapy

Summary:

      The purpose of this study is to examine the effect of androgen deprivation therapy through
      administration of enzalutamide on preventing bladder cancer recurrences in patients with
      non-muscle invasive bladder cancer (NMIBC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects with histologically confirmed NMIBC who have undergone their TURBT.

          2. Per the European Association of Urology (EAU) guidelines, only subjects with
             "Intermediate" or "High risk" bladder cancer will be enrolled21:

             For patients with "high risk" bladder cancer, only those who undergo BCG therapy
             following their TURBT will be eligible for enrollment.

          3. Subjects who receive BCG instillations post-operatively will be eligible for
             enrollment.

          4. Subjects whose tumors are AR(+) as well as AR(-) will be included, but we will
             restrict inclusion of AR(-) subjects so that they represent no more than 1/3 of the
             total study population, or any single cohort (ie. the intermediate or high-risk
             groups).

          5. Subjects of child-bearing potential must agree to 2 acceptable forms of birth control.

        Exclusion Criteria:

          1. Subjects with "low risk" bladder cancer, as defined by the EAU guidelines21, will be
             ineligible for enrollment.

          2. Subjects with "high risk" bladder cancer who do not undergo BCG therapy following
             their TURBT will be ineligible for enrollment.

          3. Subjects who have "failed" BCG therapy in the past (had a recurrence of bladder cancer
             despite prior use of BCG) will be ineligible for enrollment.

          4. Subjects who receive an immediate post-TURBT single instillation of intravesical
             chemotherapy will be ineligible for enrollment.

          5. Subjects who receive a post-operative induction course of intravesical chemotherapy
             (ie. more than just a single immediate post-operative dose of intravesical
             chemotherapy) will be ineligible for enrollment.

          6. Subjects who undergo blue-light/fluorescence cystoscopy will be ineligible for
             enrollment.

          7. Subjects with a history of heart attack within the previous 12 months or who have
             unstable cardiovascular status will be ineligible for enrollment.

          8. Subjects who have uncontrolled hypertension (for our purposes, defined as those having
             a systolic blood pressure > 160 documented on 2 occasions despite appropriate medical
             therapy) will similarly be ineligible.

          9. Subjects with a history of venous thrombo-embolism (DVT/PE) within the past 3 years.

         10. Subjects with a history of seizure disorders, or those with a history of stroke or
             transient ischemic attacks (TIA) within the previous 12 months will be ineligible.

         11. Subjects with a history of liver disease whose hepatic enzymes, alkaline phosphatase
             or bilirubin are greater than twice the upper limit of normal will be ineligible.

         12. Subjects with kidney disease with an estimated glomerular filtration rate (eGFR) < 30
             will be ineligible.

         13. Subjects with neutropenia will be ineligible.

         14. Subjects with clinical hypogonadism, those on androgen replacement therapy, or those
             with prostate cancer or other diseases treated with various forms of hormonal therapy
             (not including 5-alpha reductase inhibitors) will also be ineligible for study
             enrollment.

         15. Subjects who have undergone therapy for any malignancy within the past 5 years except
             for basal and squamous cell carcinomas of the skin will also be ineligible.

         16. Subjects with prior histories of prostate cancer treated by definitive local therapy >
             5 years ago will only be eligible if they have had no clinical or biochemical evidence
             of recurrent prostate cancer.