Phase II, multicenter, open-label, proof of concept study of tasquinimod in patients with advanced/metastatic hepatocellular (HCC), ovarian (OC), renal cell (RCC) and gastric (GC) carcinomas.
Bibliographic record
Abstract
TPS2622 Background: Treatment resistance and disease progression are common in HCC, OC, RCC and GC. Tasquinimod is an oral, quinoline-3-carboxamide derivative that binds to S100A9, resulting in immunomodulatory, anti-angiogenic and anti-metastatic effects involving downregulation of chemokine receptor type 4 and hypoxia-inducible factor. Tasquinimod significantly improves PFS (7.6 v 3.3 mo) in patients with metastatic hormone-resistant prostate cancer (Pili, R. et al. 2011. JCO 29:4022-8) and is in an ongoing phase III program. Its unique mode of action (MOA) makes tasquinimod attractive for other indications. The primary study objective is to determine the clinical activity of tasquinimod in advanced/metastatic HCC, OC, RCC and GC. Tasquinimod has been shown to delay disease progression with limited tumor shrinkage, therefore an innovative design was proposed, with PFS rate as the main endpoint. Methods: Design: Phase II, multinational, exploratory proof of concept study to evaluate tasquinimod activity in 4 independent cohorts of patients (HCC, OC, RCC and GC) with progressive disease after standard therapy. An innovative design (Litwin S. 2007. Stat Med 26:4400-15) based on the proportion of patients who have not progressed nor died at predefined timepoints (PFS rate) will be used in each cohort independently. Patients: 110–200 patients (dependent on outcome of futility analyses) aged ≥18 yr, ECOG performance status 0 or 1 will be enrolled. Patients must have histologically confirmed and documented HCC, OC, RCC or GC and demonstrable disease progression on standard therapy. Recruitment is ongoing. Dosage: Tasquinimod will be administered as a starting dose of 0.5 mg/day, in each cohort. After 2 wks, the dose will be increased to 1 mg/day based on individual safety and tolerability. Primary endpoint: PFS rate, defined as the proportion of patients who have neither progressed nor died at 12 wks (GC), 16 wks (HCC, RCC) or 24 wks (OC). Secondary endpoints: Include OS, response rate, safety, pharmacokinetics, inflammatory and specific target biomarkers to explore comprehensively the MOA according to each disease type. Clinical trial information: NCT01743469.
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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 | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".