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A Phase 2 Study Determining Safety and Tolerability of Enzalutamide (Formerly MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

Phase 2
Open (Enrolling)
Metastatic Castration-Resistant Prostate Cancer

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Trial Information

A Phase 2 Study Determining Safety and Tolerability of Enzalutamide (Formerly MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

For the study duration, all subjects will maintain androgen deprivation with a gonadotropin
releasing hormone (GnRH) agonist or antagonist or orchiectomy. Study drug will be
administered until disease progression. Disease progression is defined as a composite
endpoint consisting of either clinical deterioration, radiographic progression or
prostate-specific antigen (PSA) progression according to the Prostate Cancer Clinical Trials
Working Group 2 (PCWG2) 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 antiandrogren):

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Nature, frequency and severity of adverse events

Outcome Time Frame:

Until documented disease progression (up to 24 months)

Safety Issue:


Principal Investigator

Associate Medical Director

Investigator Role:

Study Director

Investigator Affiliation:

Astellas Pharma Global Development


United States: Food and Drug Administration

Study ID:




Start Date:

June 2012

Completion Date:

June 2014

Related Keywords:

  • Metastatic Castration-Resistant Prostate Cancer
  • MDV3100
  • prostate
  • cancer
  • enzalutamide
  • abiraterone acetate
  • prednisone
  • Prostatic Neoplasms



MD Anderson Cancer Center Houston, Texas  77030-4096