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

NON-METASTATIC CRPC

Inclusion Criteria

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
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
Castrate levels of serum testosterone of less than or equal to 50 ng/dL
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
A life expectancy of at least 3 months

Exclusion Criteria

Distant metastases, including CNS and vertebral or meningeal involvement
Prior treatment with MDV3100
Prior treatment with abiraterone
Prior treatment with ketoconazole
Concurrent treatment with medications known to have seizure potential
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.
QTc > 450 msec
History of seizure or condition that may predispose to seizure
Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, TREATMENT-NAIVE

Inclusion Criteria

Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
Castrate levels of serum testosterone of less than or equal to 50 ng/dL
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
A life expectancy of at least 3 months

Exclusion Criteria

History of, or current metastases in the brain or untreated spinal cord compression
Prior treatment with MDV3100
Prior treatment with abiraterone
Prior treatment with ketoconazole
Concurrent treatment with medications known to have seizure potential
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.
QTc > 450 msec
History of seizure or condition that may predispose to seizure
Evidence of severe or uncontrolled systemic disease or HIV infection

METASTATIC CRPC, CHEMOTHERAPY-NAIVE, POST-ABIRATERONE

Inclusion Criteria

Histologically or cytologically proven prostate cancer with progressive disease based on either PSA or radiographic progression
Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration)
Castrate levels of serum testosterone of less than or equal to 50 ng/dL
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
A life expectancy of at least 3 months
Patients must have received a minimum of 6 months of abiraterone treatment prior to disease progression

Exclusion Criteria

History of, or current metastases in the brain or untreated spinal cord compression
Prior treatment with MDV3100
Prior treatment with ketoconazole
Concurrent treatment with medications known to have seizure potential
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.
QTc > 450 msec
History of seizure or condition that may predispose to seizure
Evidence of severe or uncontrolled systemic disease or HIV infection