Interim results from ASCENT: A double-blinded randomized study of DN-101 (high-dose calcitriol) plus docetaxel vs. placebo plus docetaxel in androgen-independent prostate cancer (AIPC)
Bibliographic record
Abstract
4516 Background: High doses of calcitriol enhance the antitumor activity of multiple classes of chemotherapy in preclinical models and showed encouraging Phase 2 results in combination with docetaxel for AIPC. DN-101 is a new high-dose oral formulation designed to conveniently and reliably deliver the high calcitriol concentrations required for cancer therapy. Methods: Patients (pts) had metastatic AIPC, testosterone < 50 ng/ml, adequate organ function, clinical or PSA progression after anti-androgen withdrawal. Pts received weekly docetaxel 36 mg/m2 iv for 3 weeks of a 4-week cycle with standard dexamethasone and either 45 μg DN-101 or placebo orally 1 day prior to docetaxel. The study was powered at 85% to detect a 20% improvement in the fraction of patients with a ≥ 50% decline in serum PSA confirmed at least 4 weeks later (PSA response rate). Results: An interim analysis with a data cut-off of 6 months (June 2004) and median follow-up of 8 months is presented. 250 pts were randomized 1:1 at 48 sites in the US and Canada. Baseline characteristics were similar for both arms. PSA responses within 6 months (the primary endpoint) occurred more frequently in pts receiving DN-101 (58%) than placebo (49%), however this trend did not reach statistical significance (Cochran-Mantel-Haenszel chi square p=0.16). 102 patients had measurable disease. Objective response rate was 28% (3 CR, 10 PR of 46) vs. 20% (1 CR, 10 PR of 56) for DN-101 vs. placebo-treated patients. Most common grade 3/4 toxicities in the DN-101 and placebo-treated arms were neutropenia (8% vs. 8%), fatigue (7% vs. 15%), and hyperglycemia (6% vs. 11%). Serious adverse events occurred less frequently in DN-101 treated pts (24% vs. 36%, p=0.038). A similar trend was observed for AEs resulting in discontinuation of docetaxel (14% vs. 22% p=0.07). Conclusions: Early results show trends that favor DN-101 with respect to PSA and measurable tumor response rate and toxicity but do not reach statistical significance. Recommendations regarding further studies of DN-101 and docetaxel in AIPC will be made when the secondary endpoints of overall and progression-free survival are mature. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novacea Aventis, Novacea Aventis, Aventis Speakers Bureau, Novacea Novacea
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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 | 0.009 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| 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".