A phase 3 randomized, placebo-controlled double-blind study of ARN-509 plus abiraterone acetate (AA) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).
Bibliographic record
Abstract
TPS5071 Background: ARN-509, a potent and selective androgen receptor (AR) antagonist, inhibits AR nuclear translocation and DNA binding (Clegg, Cancer Res. 2012). AA directly inhibits androgen biosynthesis and has been approved for the treatment of mCRPC. Although ARN-509 and abiraterone both target the AR, each works through a different mechanism: the former blocks ligand binding, the latter inhibits ligand synthesis. Importantly, lack of sensitivity to one AR-targeted therapy does not necessarily imply resistance to another (Rathkopf, AACR 2014). Inhibiting the AR through multiple mechanisms simultaneously may be more effective than single pathway inhibition and has the potential to have a significant impact on the mCRPC field. This phase 3 trial will compare radiographic progression-free survival (rPFS) in pts with chemotherapy-naïve mCRPC treated with ARN-509 in combination with AA + prednisone/prednisolone (P) vs placebo + AA + P. Methods: This multicenter, double-blind, placebo-controlled trial is enrolling men with mCRPC with progressive disease and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. Pts will be stratified by presence or absence of visceral metastases, ECOG PS, and region (European Union, North America, and rest of world) and randomized (1:1) to ARN-509 (240 mg QD) + AA (1000 mg po QD) + P (5 mg po BID) or placebo + AA + P. The primary end point is rPFS using RECIST 1.1 or PCWG2 criteria. Secondary end points are overall survival, time to long-term opioid use, time to initiation of cytotoxic chemotherapy, and time to pain progression. Population pharmacokinetics of AA and biomarker analyses will be performed. The study uses a group sequential design, including 2 interim analyses. The stratified log rank test will be used for the time-to-event analysis. An independent data monitoring committee will review safety and efficacy data. Approximately 960 pts will be randomized over 2 years in 225 sites in 18 countries. (ClinicalTrials.gov Identifier: NCT02257736) Clinical trial information: NCT02257736.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.012 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".