A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients
Condition: Metastatic Castration-Resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: enzalutamide; abiraterone acetate; prednisone
Intervention description: Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).; Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).; Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).
Intervention MeSH terms: Prednisone; Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: Male
Healthy volunteers: No
Keywords: abiraterone acetate; prednisone; enzalutamide; cancer; prostate; MDV3100

Summary:

      The purpose of this study was to explore the safety and tolerability of enzalutamide in
      combination with abiraterone acetate plus prednisone. Subjects diagnosed with cancer of the
      prostate that was getting worse and spreading to the bone despite receiving hormone treatment
      were enrolled and received study treatment until disease progression.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed adenocarcinoma of the prostate without
             neuroendocrine differentiation or small cell features

          -  Presence of metastatic disease to the bone

          -  Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH)
             analogue or orchiectomy (i.e., surgical or medical castration)

          -  Subject receiving bisphosphonate or denosumab therapy must have been on stable doses
             for at least 4 weeks prior to Day 1

          -  Progressive disease defined as one or more of the following three criteria (Note:
             subjects who received an antiandrogen must demonstrate disease progression following
             discontinuation of antiandrogen):

               -  PSA progression defined by a minimum of two rising PSA levels with an interval of
                  ≥ 1 week between each determination. The PSA value at the Screening visit should
                  be ≥ 2 ng/mL

               -  Soft tissue disease progression as defined by the Response Evaluation Criteria in
                  Solid Tumors (RECIST 1.1)

               -  Bone disease progression defined by PCWG2 criteria (two or more new lesions on
                  bone scan compared with prior scan)

          -  Subject previously treated with chemotherapy must have no more than two prior
             chemotherapy regimens for the treatment of metastatic prostate cancer

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Agree to use a double-barrier method of contraception which involves the use of a
             condom in combination with one of the following: contraceptive sponge, diaphragm, or
             cervical ring with spermicidal gel or foam, if having sex with a woman of
             child-bearing potential during the length of the study and for one week after
             abiraterone is discontinued and for at least three months after enzalutamide is
             discontinued

          -  Subject agrees not to participate in another interventional study while on treatment

        Exclusion Criteria:

          -  Known or suspected metastases in the brain

          -  Absolute neutrophil count < 1,000/μL, platelet count < 75,000/μL, and hemoglobin < 9
             g/dL (NOTE: subject may not have received any growth factors or blood transfusions
             within seven days of the hematologic laboratory values obtained at the Screening
             visit)

          -  Total bilirubin (TBL), alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) > 2.5 times the upper limit of normal

          -  Creatinine (Cr) > 2 mg/dL

          -  Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide),
             5-α reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or
             biologic therapy within 4 weeks of Day 1 visit

          -  Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks)
             of Day 1 visit, or radionuclide therapy within 8 weeks of Day 1

          -  Planned palliative procedures for alleviation of bone pain such as radiation therapy
             or surgery

          -  Structurally unstable bone lesions suggesting impending fracture

          -  History of seizure or any condition that may predispose to seizure including, but not
             limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or
             alcoholism. Also, history of loss of consciousness or transient ischemic attack within
             12 months of enrollment (Day 1 visit)

          -  Clinically significant cardiovascular disease including:

               -  Myocardial infarction within 6 months of Screening visit;

               -  Uncontrolled angina within 3 months of Screening visit;

               -  Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
                  subjects with history of congestive heart failure NYHA class 3 or 4 in the past,
                  or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a
                  screening echocardiogram or multi-gated acquisition scan (MUGA) performed within
                  three months of the Screening visit results in a left ventricular ejection
                  fraction that is ≥ 45%

               -  History of clinically significant ventricular arrhythmias (e.g., ventricular
                  tachycardia, ventricular fibrillation, torsade de pointes)

               -  Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on
                  the Electrocardiogram (ECG) > 470 msec.

               -  History of Mobitz II second degree or third degree heart block without a
                  permanent pacemaker in place

               -  Hypotension (systolic blood pressure < 86 mmHg or bradycardia with a heart rate
                  of <50 beats per minute on the ECG., unless pharmaceutically induced and thus
                  reversible (i.e. beta blockers).

               -  Uncontrolled hypertension as indicated by a resting systolic blood pressure >170
                  mmHg or diastolic blood pressure >105 mmHg

          -  Prior use of ketoconazole, abiraterone acetate or enzalutamide, or participation in a
             previous clinical trial of ketoconazole, abiraterone acetate or enzalutamide

          -  History of significant bleeding disorder unrelated to cancer, including:

               -  Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

               -  Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor
                  VIII antibodies) of Screening visit

               -  History of GI bleeding within 6 months of Screening visit

          -  Active or symptomatic viral hepatitis or chronic liver disease

          -  Known history of pituitary or adrenal dysfunction