A Trial of Androgen Deprivation, Docetaxel, and Enzalutamide for Metastatic Prostate Cancer
Condition: Prostate Cancer; Prostate Adenocarcinoma
MeSH terms: Prostatic Neoplasms
Intervention: ADT+Docetaxel+Enzalutamide
Intervention description: combination therapy as listed above
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study with the combination of androgen deprivation therapy (ADT) and docetaxel with
      the addition of enzalutamide in the treatment of subjects with metastatic prostate cancer.
      The purpose of this study is to assess if ADT + docetaxel + enzalutamide is well tolerated
      and demonstrates improved efficacy compared to ADT + docetaxel.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without
             evidence of small cell carcinoma or greater than 50% neuroendocrine differentiation.
             Metastatic disease must be present including soft tissue, and/or bone metastases OR
             nonregional lymph node involvement prior to study enrollment. If the subject has
             regional lymph node involvement, there must be at least one additional site of disease
             including visceral, non-regional nodal or skeletal metastases.

          -  ADT with surgical castration with bilateral orchiectomy or medical castration with
             LHRH agonist or LHRH antagonist therapy may have been initiated no greater than 112
             days (16 weeks) prior to enrollment date. Subjects who initiated ADT prior to consent,
             are not eligible if PSA has risen ≥ 25% and ≥ 2 ng/ml above nadir value since
             initiation of ADT prior to consent.

          -  At least one PSA level of ≥ 5 ng/ml within 90 days prior to consent.

          -  Prior ADT for non-metastatic disease with LHRH agonist or LHRH antagonist therapy in
             the neoadjuvant/adjuvant setting is permitted if:

               1. Total duration of therapy did not exceed 36 months

               2. 6 months have elapsed since completion of therapy prior to consent,

               3. Serum testosterone > 50 ng/dl within 28 days prior to reinitiation of ADT for
                  metastatic disease

               4. Prior ADT for non-metastatic disease must have accompanied definitive local
                  therapy for curative intent.

          -  Age ≥ 18 years.

          -  ECOG performance status 0-2.

          -  Adequate liver function: AST and ALT <1.5x upper limit of normal, total bilirubin < 1x
             upper limit of normal.

          -  Adequate bone marrow function: Platelets >100,000 cells/mm3, Hemoglobin > 8.0g/dL and
             ANC > 1,500 cells/mm3.

          -  Adequate renal function with a creatinine clearance (based on Cockcroft-Gault formula)
             ≥ 30 mL/min.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Able to swallow and retain oral medication

        Exclusion Criteria:

          -  Personal history of seizure.

          -  Personal history of conditions that may predispose to seizure activity including
             cortical cerebrovascular accident or brain trauma.

          -  Known central nervous system metastases, including involvement of brain parenchyma and
             leptomeninges.

          -  Personal history of any condition that may impair absorption of enzalutamide.

          -  Prior or current therapy with ketoconazole, abiraterone, enzalutamide, apalutamide
             (ARN-509, JNJ-56021927), darolutamide (ODM-201, BAY1841788) or cytotoxic chemotherapy
             such as docetaxel, cabazitaxel, cyclophosphamide.

          -  Prior therapy with bicalutamide, nilutamide or flutamide within 14 days of enrollment.

          -  Within 28 days of major surgery and/or lack of recovery from prior surgical procedure
             or 14 days of palliative radiation prior to enrollment.

          -  Prior or current therapy with an investigational agent for metastatic prostate cancer.

          -  Known hypersensitivity to drugs formulated with polysorbate 80.

          -  Personal history of posterior reversible encephalopathy syndrome.

          -  CTCAE version 4.0 grade 2-4 peripheral sensory neuropathy.

          -  Human immunodeficiency virus infection or active hepatitis B or C infection.

          -  Uncontrolled and current 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 in the opinion of the investigator.

          -  Presence of any of the following within the previous 3 months prior to enrollment:
             myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
             graft, congestive heart failure, or cerebrovascular accident including transient
             ischemic attack.

          -  History of an additional active malignancy within 12 months prior to the date of
             consent (except non-melanoma skin cancer).

          -  Current use of strong CYP2C8 inhibitors, CYP3A4 inducers or CYP3A4, CYP2C9 or CYP2C19
             substrates with a narrow therapeutic range as listed in Section 7.2.1.

          -  Any condition that requires the use of prednisone > 10mg daily, or equivalent daily
             glucocorticoid dose, for greater than 14 days