Randomized phase II study of docetaxel with or without ramucirumab (IMC-1121B) or icrucumab (IMC-18F1) in patients with urothelial transitional cell carcinoma (TCC) following progression on first-line platinum-based therapy.
Bibliographic record
Abstract
TPS4675^ Background: The vascular endothelial growth factor (VEGF) pathway may play an important role in the pathogenesis of bladder cancer. Two antibodies (ramucirumab or icrucumab) in combination with docetaxel are being tested in this clinical study. Ramucirumab is a fully human IgG1 monoclonal antibody (MAb) that specifically binds with high affinity to VEGF receptor-2 (VEGFR-2), thereby blocking the interaction of VEGF ligands. Ramucirumab inhibits VEGF-mediated proliferation of human endothelial cells and migration of human leukemia cells. Icrucumab is a fully human IgG1 MAb that specifically binds with high affinity to VEGFR-1 and blocks the binding of VEGF-A, VEGF-B, and placental growth factor (PlGF) to the receptor, thereby inhibiting subsequent signaling. Blockage of VEGFR-1 and VEGFR-2 by antibodies demonstrates antiangiogenic and antitumor activity and prevents dissemination and growth of lung metastases in several tumor xenograft models. Methods: This study includes patients (pts) with TCC with progressive disease after prior platinum-based therapy. Pts are randomized equally to 1 of 3 open-label treatments given on a 21-day cycle: docetaxel (75 mg/m2) on Day 1 (Arm A); docetaxel on Day 1 and ramucirumab (10 mg/kg) on Day 1 (Arm B); or docetaxel on Day 1 and icrucumab (12 mg/kg) on Days 1 and 8 (Arm C). Randomization is stratified by the absence/presence of visceral metastases and receipt of prior antiangiogenic therapy. The primary endpoint is progression-free survival (PFS). Secondary outcome measures include response rate and duration of response, overall survival, and pharmacodynamic markers, including circulating levels of PlGF, VEGF-A, VEGF-B, soluble VEGFR-1, and soluble VEGFR-2. Exploratory analyses of VEGF, VEGFR-1, and VEGFR-2 genetic polymorphisms will be performed. As of 12 January 2012, approximately 20% of 138 planned pts were randomized in the US and Canada. The sample size will allow differentiation of an expected increase in median PFS from 3.0 months to 4.5 months with a one-sided alpha of 0.1 and a power of 71%. ClinicalTrials.gov identifier: NCT01282463.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.007 | 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".