Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)
Prostate Cancer
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Non-Metastatic, Rising PSA, Castration-Resistant, Treatment-Naive, Post-abiraterone
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Dose Escalation Cohort (Phase 1)
Non-metastatic CRPC (Phase 2)
Treatment-naive metastatic CRPC (Phase 2)
Post-abiraterone metastatic CRPC (Phase 2)
ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily. Once Recommended Phase 2 Dose (RP2D) has been selected, Phase 1 participants being treated at the lower dose levels will be allowed to escalate to the RP2D level at the discretion of the primary investigator.
Participants with non-metastatic, treatment-naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) will be enrolled. ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.
Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.
Participants with metastatic CRPC that are chemotherapy-naive, but have been previously treated with abiraterone will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.