Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide Liquid; Enzalutamide Capsule
Intervention description: Enzalutamide liquid formulation given orally (160mg); Enzalutamide gel capsule (4X 40mg)
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Castration Resistant Prostate Cancer; Androgen Receptor

Summary:

      Background:

      Enzalutamide is given to treat metastatic prostate cancer. But it takes 4 pills to deliver
      the effective dose. This can be difficult for people already taking multiple drugs. And
      swallowing may be difficult for some people. Researchers want to test out a new way of giving
      enzalutamide by mouth. They want to see if giving a person the liquid taken from inside the
      standard 4 gelatin capsules is handled by the body in the same way as giving them the
      capsules whole.

      Objectives:

      To compare how capsule and liquid forms of enzalutamide are handled by people with prostate
      cancer.

      Eligibility:

      Men at least 18 years old with prostate cancer

      Design:

      Participants will be screened with a heart test (electrocardiogram), medical history, and
      physical exam. A tissue sample or lab reports will be reviewed.

      During the study, participants will repeat screening tests and have urine tests.

      Participants will be randomly assigned to get the study drug in one of two orders: either the
      as capsules then the liquid form (Arm A) or as the liquid form then the capsule form (Arm B).

      Participants will be counseled about birth control.

      The study will have 2 periods with a minimum 42 day break in between.

      On Day 1 of Period 1 and Day 1 of Period 2, participants will be admitted to the hospital.
      They will get one dose of the study drug. They cannot eat or drink anything except water for
      at least 10 hours before and for 4 hours after the study drug. Their blood will be sampled
      over 24 hours. Lunch and dinner will be served. Participants will answer questions after
      taking the liquid form.

      Participants will have blood drawn on Day 3, Day 8, and Day 42.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically or cytologically confirmed prostate cancer.

        Note: If histopathological documentation is unavailable, a clinical course consistent with
        prostate cancer is acceptable.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Patients must have adequate organ and marrow function as defined below:

               -  Hemoglobin greater than or equal to 9 g/dL

               -  leukocytes greater than or equal to 3000/mcL

               -  absolute neutrophil count greater than or equal to 1500/mcL

               -  platelets greater than or equal to 150000/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 X institutional upper limit of normal

               -  creatinine within normal institutional limits

        OR

        --creatinine clearance greater than or equal to 30 mL/min/1.73 m^2 for patients with
        creatinine levels above institutional normal (calculated via Cockcroft-Gault equation)

          -  Patients must not have other concurrent malignancies (within the past 2 years with the
             exception of non-melanoma skin cancer and Rai Stage 0 chronic lymphocytic leukemia),
             in situ carcinoma of any site, or life threatening illnesses, including untreated
             infection (must be at least 1 week off intravenous antibiotic therapy before beginning
             enzalutamide).

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

          -  Willingness to travel to National Institutes of Health (NIH) for follow-up visits.

          -  Men age greater than or equal to 18 years of age. Children are excluded because
             prostate cancer is not common in pediatric populations. Women are not eligible because
             this disease occurs only in men

          -  The effects of enzalutamide on the developing human fetus are unknown. For this reason
             men must agree to use adequate contraception (hormonal or barrier method of birth
             control; abstinence) throughout the course of the study and for 3 months after the
             last dose. 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.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents (in the past 28 days) or
             herbal medications (within 7 days).

          -  Patients must not be on enzalutamide within five half-lives before the first planned
             dose of the study drug or anticipating to start enzalutamide within the next 3 months
             of the first planned dose of study drug

          -  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).

          -  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 who are taking medications that may alter the metabolism of enzalutamide.
             This includes the following: strong or moderate cytochrome P450 family 2 subfamily C
             member 8 (CYP2C8) inhibitors or inducers; strong cytochrome P450 family 3 subfamily A
             member 4 (CYP3A4) inhibitors or inducers; or Cytochrome P450 2C9 (CYP2C9), 2C19 or 3A4
             substrates with a narrow therapeutic index.

          -  History of seizure, including any febrile seizure, loss of consciousness, or transient
             ischemic attach, or any condition that may pre-dispose to seizure (e.g. prior stroke,
             brain arteriovenous malformation, head trauma with loss of consciousness requiring
             hospitalization).