Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

NON-METASTATIC CRPC

Inclusion Criteria

1. Histologically or cytologically proven prostate cancer with high risk for development
of metastases, defined as either a PSA value >=8 ng/mL within the last 3 months or PSA
Doubling Time <=10 months

2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH)
analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)

3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. A life expectancy of at least 3 months

Exclusion Criteria

1. Distant metastases, including CNS and vertebral or meningeal involvement

2. Prior treatment with MDV3100

3. Prior treatment with abiraterone

4. Prior treatment with ketoconazole

5. Concurrent treatment with medications known to have seizure potential

6. Concurrent treatment with corticosteroids. If they are already on steroids, patients
will be allowed to enroll on the study but will need to taper off as soon as possible.

7. QTc > 450 msec

8. History of seizure or condition that may predispose to seizure

9. Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, TREATMENT-NAIVE

Inclusion Criteria

1. Histologically or cytologically proven prostate cancer with progressive disease based
on either PSA or radiographic progression

2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH)
analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)

3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. A life expectancy of at least 3 months

Exclusion Criteria

1. History of, or current metastases in the brain or untreated spinal cord compression

2. Prior treatment with MDV3100

3. Prior treatment with abiraterone

4. Prior treatment with ketoconazole

5. Concurrent treatment with medications known to have seizure potential

6. Concurrent treatment with corticosteroids. If they are already on steroids, patients
will be allowed to enroll on the study but will need to taper off as soon as possible.

7. QTc > 450 msec

8. History of seizure or condition that may predispose to seizure

9. Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, CHEMOTHERAPY-NAIVE, POST-ABIRATERONE

Inclusion Criteria

1. Histologically or cytologically proven prostate cancer with progressive disease based
on either PSA or radiographic progression

2. Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH)
analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)

3. Castrate levels of serum testosterone of less than or equal to 50 ng/dL

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

5. A life expectancy of at least 3 months

6. Patients must have received a minimum of 6 months of abiraterone treatment prior to
disease progression

Exclusion Criteria

1. History of, or current metastases in the brain or untreated spinal cord compression

2. Prior treatment with MDV3100

3. Prior treatment with ketoconazole

4. Concurrent treatment with medications known to have seizure potential

5. Concurrent treatment with corticosteroids. If they are already on steroids, patients
will be allowed to enroll on the study but will need to taper off as soon as possible.

6. QTc > 450 msec

7. History of seizure or condition that may predispose to seizure

8. Evidence of severe or uncontrolled systemic disease or HIV infection