Mature results of a randomized phase II study of OGX-011 in combination with docetaxel/prednisone versus docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer
Bibliographic record
Abstract
5012 Background: Clusterin is a cytoprotective chaperone protein associated with CRPC progression. OGX is a 2'-methoxyethyl antisense that potentiates chemotherapy in xenografts and inhibits clusterin expression at doses of <640 mg. Methods: Pts with CRPC and chemo-naive received docetaxel (DOC) 75mg/m 2 q3w + OGX 640mg IV weekly + prednisone (Arm A) or DOC + prednisone (Arm B) in a single stage randomized phase II design. Primary endpoint was PSA response rate (RR). Progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Planned sample size was 40/arm: Arm A the hypotheses (PSA RR<40% vs. >60%) could be tested at 10% β and 10% α, Arm B the true PSA RR could be estimated with half-width of the 90% CI<13% if PSA RR=40%. Results: 82 pts (41 Arm A, 41 Arm B) were randomized from 09/05–12/06. At this analysis time, all pts are off therapy and 49 have died. One pt was ineligible but included in ITT survival analysis. Baseline characteristics were similar: median age 69 (49–87), PSA >100 μg/L in 51%, Hgb ≥100 g/L in 98%, alk phos >ULN in 44%, LDH >ULN in 36%, ECOG performance status (PS) 0:1 in 51%:49%, bone/lymph node/visceral metastases in 69%/50%/28%. Median cycles for Arm A and B was 9 and 7. Adverse events associated with OGX included fatigue, fever, rigors, diarrhea and rash. Mean serum clusterin change on day 1 cycle 2 was -18% in Arm A and +8% in Arm B (p = 0.0005). PSA RR was 58% (Arm A) and 54% (Arm B). PSA declines at 12 weeks of any/>30%/>50% was observed in 87%/65%/45% (Arm A) and 68%/58%/34% (Arm B). PSA/objective disease progression as best response occurred in 0%/4% (Arm A), and 3%/17% (Arm B). PFS for Arms A and B was 7.3 (5.3–8.8) and 6.1 months (3.7–8.6). Median OS for Arms A and B was 27.5 (19.2-∞) and 16.9 months (12.7–26.0) (unadjusted HR = 0.60 [0.34–1.06], p = 0.07). Variables predictive of OS on multivariate analysis: PS 0 vs 1 (p = 0.0002), presence of visceral metastasis (p = 0.006) and treatment assignment (HR = 0.54 [0.29–0.97], p = 0.04). Conclusions: The PSA RR in both arms met criterion for further study. OGX reduced serum clusterin and OS appears superior with DOC/OGX. This combination warrants further evaluation. Supported by a grant from the NCI-Canada/Canadian Cancer Society. [Table: see text]
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".