A Study to Assess the Benefit of Treatment Beyond Progression With Enzalutamide in Men Who Are Starting Treatment With Docetaxel After Worsening of Their Prostate Cancer When Taking Enzalutamide Alone
Condition: Metastatic Castration Resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Enzalutamide; Docetaxel; Prednisolone; Placebo
Intervention description: Oral; intravenous infusion; Oral; Oral
Intervention MeSH terms: Prednisolone; Docetaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 688.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Castration-resistant; Docetaxel; Chemotherapy- Naïve; Enzalutamide; Prostate Cancer; Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer; Prednisolone; Xtandi; Metastatic Castration Resistant Prostate Cancer

Summary:

      The purpose of the study was to understand if there was benefit in continued treatment with a
      medicine called enzalutamide, when starting treatment with docetaxel and prednisolone (a
      standard chemotherapy for prostate cancer), after the prostate cancer had gotten worse when
      treated with enzalutamide alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate without neuroendocrine
             differentiation or small cell features;

          -  Ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing
             hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of
             initiation of investigational medicinal product (IMP), or bilateral orchiectomy (i.e.,
             surgical or medical castration);

          -  Metastatic disease documented by at least 2 bone lesions on bone scan, or soft tissue
             disease documented by computed tomography (CT)/magnetic resonance imaging (MRI);

          -  Progressive disease at study entry defined as the following occurring in the setting
             of castrate levels of testosterone: Prostate specific antigen (PSA) progression
             defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between
             each determination.

          -  Asymptomatic or minimally symptomatic prostate cancer (Brief Pain Inventory - Short
             Form (BPI-SF) question 3 score of < 4);

          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;

          -  Estimated life expectancy of ≥ 12 months;

          -  Be suitable and willing to receive chemotherapy as part of the trial;

          -  Able to swallow the IMP and comply with study requirements;

          -  Subject agreed not to participate in another interventional study while on treatment.

        Exclusion Criteria:

          -  Prior treatment with the following agents for the treatment of prostate cancer:
             Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a
             clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory
             therapies; Cytotoxic chemotherapy; Participation in a clinical trial of an
             investigational agent that inhibits the AR or androgen synthesis unless the treatment
             was placebo;

          -  Current or prior treatment within 4 weeks prior to initiation of investigational
             medicinal product (IMP) with the following agents for the treatment of prostate
             cancer: Antiandrogens; 5-α reductase inhibitors; Estrogens; Anabolic steroids; Drugs
             with antiandrogenic properties; Progestational agents;

          -  Subject had received investigational therapy within 28 days or 5 half-lives whichever
             was longer, prior to initiation of IMP;

          -  Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to
             initiation of IMP;

          -  Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation
             of IMP;

          -  Major surgery within 4 weeks prior to initiation of IMP;

          -  History of seizure or any condition that may predispose to seizures at any time in the
             past. History of loss of consciousness or transient ischemic attack within 12 months
             prior to Screening;

          -  Known or suspected brain metastasis or active leptomeningeal disease;

          -  History of another malignancy within the previous 5 years other than non-melanoma skin
             cancer;

          -  Clinically significant cardiovascular disease;

          -  Gastrointestinal disorders affecting absorption;

          -  Medical contraindications to the use of prednisolone or docetaxel;

          -  Allergies to any of the active ingredients or excipients in the study drugs