Using Multiparametric MRI to Evaluate Intraprostatic Tumor Responses and Androgen Resistance Patterns in Newly Diagnosed Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Goserelin; Enzalutamide; mpMRI
Intervention description: 10.8mg administered subcutaneously every 12 weeks (2 doses); 160mg orally, daily for 24 weeks; Multiparametric MRI - One at baseline and after 6 months of treatment
Intervention MeSH terms: Goserelin
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiparametric MRI; Prostatectomy; Focal Prostate Cancer; Normal Testosterone; Non-Metastatic

Summary:

      Background:

        -  There are several ways to treat prostate cancer. Researchers want to see how well a
           certain kind of imaging helps detect prostate cancer. They also want to see if a
           particular drug combination used before surgery will benefit people with prostate cancer
           that hasn't spread in the body (non-metastatic). The combination will be androgen
           deprivation therapy and enzalutamide.

        -  The combination of androgen deprivation therapy and enzalutamide has been shown to make
           patients with advanced (metastatic disease) live longer. The investigators want to see
           if using it earlier can increase cure rate of surgery and identify genetic or molecular
           characteristics that are associated with better outcomes.

      Objectives:

      - To develop better ways of detecting prostate cancer before and after pre-operative
      treatment.

      Eligibility:

      - Men at least 18 years old with non-metastatic prostate cancer. They must be candidates for
      a radical prostatectomy.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood tests. They
           will have scans and X-rays.

        -  Before starting the study drugs, participants will have:

        -  Vital signs taken, medical history, and blood tests.

        -  Electrocardiogram (ECG) heart test, with patches stuck on the skin.

        -  Small piece of tumor removed (biopsy) using image guidance from magnetic resonance
           imaging (MRI) and ultrasound.

        -  3T multi-parametric magnetic resonance imaging (mpMRI). Participants will lie on a table
           that slides into a metal cylinder. A probe will be inserted in the rectum. They will be
           in the scanner for about 60 minutes, lying still. The scanner makes loud knocking
           sounds. Participants will get earplugs.

        -  Participants will take the 2 study drugs for 6 months.

        -  Enzalutamide is taken as 4 pills once a day.

        -  Androgen deprivation therapy is given by injection 2 times over 6 months.

        -  During these 6 months, participants will visit the clinic monthly. They will have
           physical exam, vital signs, and blood drawn.

        -  After finishing the study drugs, participants will have another 3T mpMRI. Then they will
           have prostate removal surgery.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically or cytologically confirmed prostate cancer confirmed
             by the Laboratory of Pathology, National Cancer Institute (NCI) or Pathology
             Department at Walter Reed Bethesda

          -  Must have previously untreated (with definitive therapy) prostate cancer with
             intermediate or high risk features defined as:

               -  Intermediate risk:

                    -  Prostate-specific antigen, (PSA) level is between 10 and 20 ng/ml or

                    -  Gleason score is 7 or

                    -  Stage T2b or T2c

               -  High Risk:

                    -  Gleason 8 and higher OR

                    -  PSA greater than 20 at the time of diagnosis OR

                    -  Seminal vesicle involvement OR

                    -  Possible (on magnetic resonance imaging (MRI) Extra-capsular extension (T3
                       disease)

          -  Patients must be eligible for and must be planning to undergo radical prostatectomy

          -  Patients must have testosterone levels greater than or equal to 100 ng/dL

          -  Men age greater than or equal to 18 years.

               -  Children are excluded because prostate cancer is not common in pediatric
                  populations.

               -  Women are not eligible because this disease occurs only in men.

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

          -  Patients must have normal organ and marrow function as defined below:

          -  Hemoglobin greater than or equal to 9 g/dL

          -  leukocytes greater than or equal to 3,000/mcL

          -  absolute neutrophil count greater than or equal to 1,500/mcL

          -  platelets greater than or equal to 150,000/mcL

          -  total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase(SGOT)/Alanine
             aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT) less than or equal
             to 3 X institutional upper limit of normal

          -  creatinine within normal institutional limits

        OR

          -  creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with
             creatinine levels above institutional normal.

          -  The effects of enzalutamide on the developing human fetus are unknown. For this reason
             and because androgen receptor antagonists as well as other therapeutic agents used in
             this trial are known to be teratogenic, male participants and their female partners of
             child bearing potential must agree to use adequate contraception (hormonal or barrier
             method of birth control; abstinence). Male participants should use a condom if having
             intercourse with a pregnant woman. Additionally, a condom plus another effective
             method of birth control is recommended during therapy and for 3 months after treatment
             for male participants having intercourse with a woman of reproductive potential.
             Should a woman become pregnant or suspect she is pregnant while her partner is
             participating in this study, she should inform her treating physician immediately.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

          -  Willingness to undergo biopsy.

          -  Ability to detect lesions within prostate on magnetic resonance imaging (MRI) for
             biopsy

          -  Willingness to travel to National Institutes of Health (NIH) for follow-up visits.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents (in the past 28 days) or
             herbal medications (within 1 day).

          -  Patients with distant metastatic disease beyond N1(regional) lymph nodes on
             conventional imaging studies (Computed tomography (CT), MRI or Bone Scan).

          -  Patients who have received any prior therapy for prostate cancer with surgery,
             radiation, and/or chemotherapy

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to enzalutamide or other agents used in study.

          -  Clinically significant cardiac disease, e.g. New York Heart Association (NYHA) classes
             III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension,
             myocardial infarction in the previous 6 months as confirmed by an electrocardiogram
             (ECG).

          -  Contraindication to biopsy:

               -  Bleeding disorders

               -  Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to
                  1.5 times the upper limit of normal

               -  Artificial heart valve

          -  Contraindication to MRI:

               -  Patients weighing more than weight limit for the scanner tables

               -  Allergy to MR contrast agent

               -  Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable
                  electronic device

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients with known human immunodeficiency virus (HIV) are eligible. These patients
             are at increased risk of lethal infections when treated with marrow-suppressive
             therapy. In addition, if patients are receiving combination antiretroviral therapy,
             there is potential for pharmacokinetic interactions with enzalutamide. Appropriate
             studies will be undertaken in patients receiving combination antiretroviral therapy
             when indicated.

          -  Patients with known active treatment for Hepatitis B and C infections.

          -  Patients who are taking medications that are strong inhibitors of Cytochrome P450 3A4
             (CYP3A4) or P-glycoprotein (PgP) and need to remain on these medications. For a
             current table of Substrates, Inhibitors and Inducers please access the following
             website:

        http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLa
        beling/ucm093664.htm

          -  History of seizure, including any febrile seizure, loss of consciousness, or transient
             ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke,
             brain arteriovenous malformation, head trauma with loss of consciousness requiring
             hospitalization).

          -  Other medications used for urinary symptoms including 5-alpha reductase inhibitors
             (finasteride and dutasteride) and alternative medications known to alter prostate
             specific antigen (PSA) (eg phytoestrogens and saw palmetto) cannot be taken while
             patients are receiving enzalutamide

          -  Patients with a malignancy within the past 3 years for which study drugs or a
             prostatectomy is a contraindication.