A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
Condition: Metastatic Castration Resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide
Intervention description: Participants were administered four 40-mg capsules orally once daily and taken as close to the same time each day as possible and could be taken with or without food.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Xtandi; Metastatic Castration Resistant Prostate Cancer; Metastatic; Prostate Cancer; Chemotherapy; Castration-resistant; Enzalutamide

Summary:

      The purpose of the study was to understand if there is benefit in treatment with a medicine
      called enzalutamide in the re-treatment setting. Patients must have been previously treated
      with enzalutamide in the pre-chemotherapy setting for a minimum of 8 months and have disease
      progressed, followed by docetaxel and/or cabazitaxel for at least 4 cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without
             signet ring cell features.

          -  Presence of metastatic disease (M1) as assessed by computed tomography/ magnetic
             resonance imaging (CT/MRI) and/or whole-body radionuclide bone scan.

          -  Subject has been previously treated with enzalutamide for at least 8 months, and
             stopped enzalutamide due to progressive disease (not due to adverse events), followed
             by at least 4 cycles of docetaxel and/or cabazitaxel chemotherapy, with or without
             other intervening anti-cancer therapies (including but not limited to
             aminoglutethimide, ketoconozole, abiraterone acetate, Rad-223, or sipuleucel-T), prior
             to receiving chemotherapy. Note: for patients who receive sequential taxanes, there
             must not have been progressive disease upon ending the first taxane, or use of any
             anti-cancer agents between the two taxanes.

          -  Ongoing androgen deprivation therapy with an gonadotropin releasing hormone (GnRH)
             analogue or prior bilateral orchiectomy (medical or surgical castration). For patients
             who have not had bilateral orchiectomy, there must be a plan to maintain effective
             GnRH-analogue for the duration of the trial.

          -  Testosterone ≤ 1.73 nmol/L (≤ 50 ng/dL) at screening.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening.

          -  Estimated life expectancy of ≥ 6 months at screening.

          -  Ability to swallow study drugs and to comply with study requirements throughout the
             study.

          -  Throughout study, male subject and a female partner who is of childbearing potential
             must use 2 acceptable methods of birth control (1 of which must include a condom
             barrier method of contraception) starting at screening and continuing throughout the
             study period and for 3 months after final study drug administration. Two acceptable
             methods of birth control thus include the following:

               -  Condom (barrier method of contraception) AND

               -  One of the following is required:

               -  Established use of oral, injected, or implanted hormonal method of contraception
                  by the female partner performed at least 6 months before screening;

               -  Placement of an intrauterine device or intrauterine system by the female partner;

               -  Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with
                  spermicidal foam/gel/film/cream/suppository by the female partner;

               -  Tubal ligation in the female partner.

               -  Vasectomy or other procedure resulting in infertility (e.g., bilateral
                  orchiectomy), performed at least 6 months before screening

          -  Must not donate sperm from screening through 3 months after final study drug
             administration.

        Exclusion Criteria:

          -  Known or suspected neuroendocrine/small cell feature.

          -  Use of any antineoplastic treatment post-chemotherapy, including but not limited to
             aminoglutethimide, ketoconozole, abiraterone acetate, Rad-223, sipuleucel-T, or
             enzalutamide. Continuing steroids is permitted.

          -  Palliative radiation therapy within 2 weeks of Day 1, or within 4 weeks of Day 1 if a
             radionuclide was utilized.

          -  Use of an investigational agent within 4 weeks of Day 1 visit.

          -  Major surgery within 4 weeks prior to Day 1 visit.

          -  History of seizure or any condition that may predispose to seizures (e.g., prior
             cortical stroke or significant brain trauma) at any time in the past. History of loss
             of consciousness or transient ischemic attack within 12 months of screening.

          -  History of clinically significant cardiovascular disease including:

               -  Myocardial infarction or uncontrolled angina within 3 months;

               -  History of congestive heart failure New York Heart Association (NYHA) class 3 or
                  4 in the past, unless a screening echocardiogram or multi-gated acquisition scan
                  performed within three months results in a left ventricular ejection fraction
                  that is ≥ 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.

          -  Clinically significant cardiovascular disease at screening including:

               -  Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury
                  (mm Hg) at screening;

               -  Bradycardia as indicated by a heart rate of < 45 beats per minute on the
                  screening electrocardiogram (ECG) and on physical examination;

               -  Uncontrolled hypertension as indicated by at least 2 consecutive measurements of
                  a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105
                  mmHg at the screening visit.

          -  Subject has a known or suspected hypersensitivity to enzalutamide or any components of
             the formulation used.

          -  Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
             investigator, would make the patient inappropriate for enrollment.

          -  Known or suspected brain metastasis or leptomeningeal disease.

          -  Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer
             disease within last 3 months).

          -  Absolute neutrophil count < 1,500/μL, platelet count < 75,000/μL, or hemoglobin < 5.6
             mmol/L (9 g/dL) at screening.

          -  Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
             ≥ 2.5 times upper limit of normal (ULN) at screening.

          -  Creatinine > 177 μmol/L (> 2 mg/dL) at screening.

          -  Albumin < 30 g/L (3.0 g/dL) at screening.

          -  Treatment with abiraterone acetate prior to enzalutamide for metastatic castration -
             resistant prostate cancer (mCRPC) in the prechemotherapy setting. (Note: Patients who
             have received concomitant enzalutamide and abiraterone acetate therapies are not
             excluded).