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

Phase 1

Active, not recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: ARN-509 (Phase 1); Drug: ARN-509 (Phase 2)

• Registration Number: NCT01171898
• Lead Sponsor: Aragon Pharmaceuticals, Inc.

Brief Summary

The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-26
• Study First Submitted: 2010-07-27
• Study First Submitted QC: 2010-07-27
• Study First Posted: 2010-07-29
• Primary Completion: 2012-08-20
• Disposition First Submitted: 2014-01-24
• Disposition First Submitted QC: 2014-01-24
• Disposition First Posted: 2014-05-07
• Results First Submitted: 2018-05-08
• Results First Submitted QC: 2018-07-02
• Results First Posted: 2018-07-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-22
• Last Update Posted: 2025-05-25
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 127

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Escalation Cohort (Phase 1)	ARN-509 (Phase 1)	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.
Non-metastatic CRPC (Phase 2)	ARN-509 (Phase 2)	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.
Treatment-naive metastatic CRPC (Phase 2)	ARN-509 (Phase 2)	Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.
Post-abiraterone metastatic CRPC (Phase 2)	ARN-509 (Phase 2)	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.

Primary Outcome Measures

Name	Time	Method
Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12	Week 12	Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Phase 1 and 2: Objective Response Rate	Up to approximately 7 years	Objective Response Rate was defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). Where, CR defined as disappearance of all target lesions. Any pathological lymph nodes must had reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions. Confirmed responses were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response.
Phase 1 and 2: Median Time to PSA Progression	Up to approximately 7 years	Time to PSA progression was measured as the time interval from the date of the first dose to the date of PSA progression as defined by the PCWG2 criteria. PCWG2 criteria: For participants who achieved \>=50% decrease from the baseline PSA, assessment of time to disease progression was when the PSA increased 25% and at a minimum of 2 ng/mL above the nadir at 3 or more weeks later. For participants without a PSA decrease, the time for progression was calculated at the time when the PSA progression was \>=25% and \>=2 ng/mL after 12 weeks.
Phase 2: Median Metastasis-Free Survival (MFS)	Up to approximately 7 years	MFS was defined as the time from the start of treatment until new metastatic lesions were observed on Computed Tomography/ Magnetic Resonance Imaging (CT/MRI) scans or radionuclide bone scans (according to PCWG2 criteria: appearance of \>=2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that showed at least 2 or more additional new lesions) or death, whichever occurred first.
Phase 1 and 2: Progression-free Survival (PFS)	Up to approximately 7 years	PFS was defined as the time from randomization to the radiographic disease progression or death, whichever occurred first. Radiographic progression defined by at least one of the following: a) Soft tissue progression by modified RECIST confirmed on repeat imaging \>= 6 weeks later; b) Progression by bone scans: 1) first bone scan with \>= 2 new lesions compared to baseline observed \<12 weeks from start date and confirmed on a second bone scan \>=6 weeks later that showed \>=2 additional lesions (a total of \>=4 new lesions compared to baseline); or 2) first bone scan with \>=2 new lesions compared to baseline observed \>=12 weeks from start date and the new lesions verified on the next bone scan \>=6 weeks later (a total of \>=2 new lesions compared to baseline).