Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial.
Bibliographic record
Abstract
TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017.
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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) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 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".