Enzalutamide + External Beam Rt For Prostate
Condition: Intermediate Risk Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; External Beam Radiation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Intermediate Risk Prostate Cancer

Summary:

      This research study is evaluating a drug called enzalutamide in combination with external
      beam radiation therapy as a possible treatment for prostate cancer. Presently, when
      participants receive hormonal therapy with radiation therapy for prostate cancer, medications
      are given to reduce testosterone levels in the blood stream. This leads to side effects such
      as loss of sex drive, erectile dysfunction (ED) and decrease in muscle strength. The purpose
      of this study is test another form of hormonal therapy with radiation therapy. The medication
      called enzalutamide will be used with radiation therapy. Instead of lowering testosterone,
      enzalutamide blocks testosterone in cells. This study will test if enzalutamide when used
      with radiation will lower the PSA without causing the side effects associated with
      medications that lower testosterone in the blood stream.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Study population: Participants must have histologically confirmed malignancy and are
             candidates for external beam radiation therapy. Patients eligible for this study must
             have intermediate risk disease defined as PSA values between 10-20 ng/ml and/or T2b-c
             and/or Gleason grade 7. If all three are present, less than 50% of the core biopsies
             can be positive.

          -  Patients previously diagnosed with low risk (Gleason score < 6, clinical stage < T2a,
             and PSA< 10) prostate cancer undergoing active surveillance who are re-biopsied and
             found to have intermediate risk disease according to the protocol criteria are
             eligible for enrollment within 180 days of the repeat biopsy procedure.

          -  Age 18 years or more.

          -  Life expectancy of greater than 1 year.

          -  ECOG performance status ≤ 2 (see Appendix D).

          -  Participants must have normal organ and marrow function as defined below:

          -  Leukocytes ≥3,000/mcL

          -  Platelets ≥80,000/mcL

          -  Total bilirubin < 2X institutional upper limit

          -  AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

          -  Creatinine < 2x institutional limits .

          -  The effects of enzalutamide on the developing human fetus are unknown. For this reason
             and because enzalutamide may be teratogenic, men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation.

        Ability to understand and the willingness to sign a written informed consent

        Exclusion Criteria:

          -  Patients must NOT meet any of the following exclusion criteria

          -  Received an investigational agent within 4 weeks prior to enrollment

          -  Stage T4 prostate cancer by clinical examination or radiologic evaluation.

          -  Hypogonadism or severe androgen deficiency as defined by screening serum testosterone
             less than 50 ng/dL below the normal range for the institution.

          -  Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.

          -  Receiving concurrent androgens, anti-androgens, estrogens, or progestational agents,
             or received any of these agents within the 6 months prior to enrollment or having
             taken finasteride or dutasteride within 30 days of registration.

          -  History of another active malignancy within the previous 5 years other than curatively
             treated nonmelanomatous skin cancer and superficial bladder cancer. Participants
             treated for malignancy with no relapse within two years are eligible to participate in
             the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection.

          -  Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
             Investigator, would make the patient inappropriate for enrollment.

          -  Unwilling to use contraceptives while on study if relevant to patient.

          -  History of seizure or any condition or concurrent medication that may predispose to
             seizure.

          -  History of loss of consciousness or transient ischemic attack within 12 months prior
             to enrollment.

               -  Clinically significant cardiovascular disease, including:

               -  Myocardial infarction within 3 months of enrollment;

               -  Uncontrolled angina within 3 months of enrollment;

               -  Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
                  history of congestive heart failure NYHA class 3 or 4 in the past, unless a
                  screening echocardiogram or multi-gated acquisition scan performed within 3
                  months results in a left ventricular ejection fraction ≥ 45%;

               -  History of clinically significant ventricular arrhythmias (e.g., ventricular
                  tachycardia, ventricular fibrillation, torsades de pointes);

               -  History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place;

               -  Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive
                  measurements at the Screening visit;

               -  Bradycardia as indicated by a heart rate < 50 beats per minute at the Screening
                  visit;

               -  Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or
                  diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the
                  screening visit;

               -  EKG demonstrating equal to or greater than grade III toxicity according the NCI
                  Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

               -  History of gastrointestinal disorders (medical disorders or extensive surgery)
                  that may interfere with the absorption of oral study drug(s) within 3 months of
                  enrollment.

               -  Major surgery within 4 weeks of registration.

               -  Previous use, or participation in a clinical trial, of an investigational agent
                  that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683,
                  TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
                  ketoconazole.

               -  Any condition or reason that, in the opinion of the Investigator, interferes with
                  the ability of the patient to participate in the trial, places the patient at
                  undue risk, or complicates the interpretation of safety data.

               -  Need for any of the medications on the list of drugs to be used with caution or
                  to be avoided (see APPENDIX F).

               -  Use of herbal or alternative remedies that may affect hormonal status such as
                  Prostasol or PC-SPES.