| Eligibility |
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation or small cell features.
Patients with systemic prostate cancer as defined by either a) hormonal naïve metastatic
prostate cancer with radiographic evidence of visceral or osseous metastasis or b)
biochemical recurrence prostate cancer that fulfills all of the following criteria:
A minimum of three rising prostatic-specific antigen levels with an interval of =/> 1 week
between each test, The prostatic-specific antigen (PSA) value at the screening visit should
be =/> 2 ng/ml prostatic-specific antigen doubling time = 9 months.
Patients should be 65 years or older. Patients who are deemed "not fit" by comprehensive
geriatric assessment or at high risk for side effects as determined by the treating
physician. A case report form will be used to document the specifics of why each eligible
patient is not considered an ideal candidate.
Serum testosterone level > 1.7 nmol/L (50 ng/dL) at the screening visit (non- castrate).
Patients could have received hormonal therapy as part of definitive treatment for previous
localized prostate cancer. However, they should be off any hormonal therapy for greater
than six months prior to entry to clinical trial.
Eastern Cooperative Oncology Group performance status of 0 to 2. Able to swallow the study
drug and comply with study requirements.
Exclusion Criteria:
Severe concurrent disease or infection that, in the judgment of the investigator, would
make the patient inappropriate for enrollment.
Known brain metastases. Brain imaging studies are not required for eligibility if the
patient has no neurologic signs or symptoms suggestive of brain metastasis. However, if
brain imaging studies are performed, they must be negative for disease.
Patient is receiving treatment for another active malignancy excluding localized cutaneous
squamous or basal cell carcinoma.
Prior treatment for systemic prostate cancer. Prior treatment with enzalutamide. Treatment
with androgen receptor antagonists (bicalutamide, flutamide, nilutamide,), ketoconazole,
abiraterone, finasteride, dutasteride, estrogens, or chemotherapy in an adjuvant setting
within 6 months of enrollment (Day 1 visit) or plans to initiate treatment with any of
these treatments.
Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to
initiate treatment with any of these treatments during the study period.
Use of herbal products that may decrease prostatic-specific antigen levels (e.g., saw
palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of
prednisone/prednisolone per day within 4 weeks of enrollment (Day 1 visit) or plans to
initiate treatment with any of these treatments during the study.
Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and
radioisotope therapy within 8 weeks of enrollment (Day 1 visit).
Participation in a previous clinical trial of an investigational agent that blocks androgen
synthesis within six months.
Participation in a previous clinical trial of enzalutamide. Use of an investigational agent
within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with an
investigational agent during the study.
Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of
the study the following medications known to lower the seizure threshold or increase or
decrease the bioavailability of the drug.
Concomitant use of strong or moderately strong Cytochrome P450 isozyme inducers:
Strong Cytochrome P450 isoenzyme 2C8 inhibitors like gemfibrozil, Strong Cytochrome P450
isoenzyme 2C8 inducers like Rifampin, Strong Cytochrome P450 isoenzyme 3A4 inhibitors like
Itraconazole, Aminophylline/theophylline, Atypical antipsychotics (e.g., clozapine,
olanzapine, risperidone, ziprasidone), Bupropion, Class IA and Class III antiarrhythmics
(e.g., amiodarone, bretylium, disopyramide, ibutilide, procainamide, quinidine, sotalol);
Dolasetron, Droperidol, Lithium, Macrolide antibiotics (e.g., erythromycin,
clarithromycin); Pethidine, Phenothiazine antipsychotics (e.g., chlorpromazine,
mesoridazine, thioridazine); Pimozide, Tricyclic and tetracyclic antidepressants(e.g.,
amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine).
History of seizure, including any febrile seizure, loss of consciousness, or transient
ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may
predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma
with loss of consciousness requiring hospitalization).
Clinically significant cardiovascular disease including:
Myocardial infarction within 6 months, Uncontrolled angina within 3 months, Congestive
heart failure New York Heart Association class 3 or 4, or patients with history of
congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram
or multigated acquisition scan performed within 3 months results in a left ventricular
ejection fraction that is =/> 45%, hypotension (systolic blood pressure < 86 millimeters of
mercury [mmHg] or bradycardia with a heart rate < 50 beats per minute, uncontrolled
hypertension as indicated by a resting systolic blood pressure of 170 mmHg or diastolic
blood pressure > 105 mmHg at the Screening or Study Day 1 visit.
Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer
within last 3 months).
Major surgery within 4 weeks prior to enrollment (Day 1 visit). Absolute neutrophil count <
1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) at the
Screening visit; (NOTE: patients may not have received any growth factors or blood
transfusions within 7 days of the hematologic laboratory values obtained at the Screening
visit).
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