Early results of a PMH Phase II Consortium trial of AZD0530 in advanced soft tissue sarcoma (STS)
Bibliographic record
Abstract
10579 Background: AZD0530 is a novel oral anilino quinazoline that is selective for c-Src, c-Yes, Lck, and Bcr-Abl through ATP competitive and reversible inhibition of the target enzyme. Src kinases play a role in tumor cell migration, invasion and metastasis as well as being part of the signaling cascade for angiogenesis and growth factors. Advanced STS have limited therapeutic options; therefore we tested the efficacy of AZD0530 in advanced STS. Methods: The study utilized a Simon Two stage design with the primary endpoint be objective tumor response + prolonged stable disease rate (defined as partial/complete response by RECIST, or stable disease >4 months). Patients with measurable advanced STS with up to one prior chemotherapy for metastatic disease were eligible for study participation following informed consent. Patients were excluded for cardiac dysfunction, poorly controlled hypertension, inability to swallow or absorb medication. Patients had pulmonary function tests at baseline that were repeated within the first 4 weeks of therapy. Results: 17 patients (11 F, 6M) with advanced STS (leiomyosarcoma 5, rhabdomyosarcoma 3, MFH/carcinosarcoma/Fibrosarcoma 2, endometrial stromal sarcoma/liposarcoma/non-rhabdoSTS 1 each) were enrolled, the majority of whom had prior therapy (14 chemo and 9 xrt). Five continue on study. Nine discontinued therapy for progressive disease, 2 for toxicity and 1 patient request. Median time to progression in the 13 patients was 1.7 months. Possibly related severe adverse events (all grade 3) included fatigue (2), anemia/lymphopenia/hypokalemia (1 each). To date no confirmed responses have been seen. No drug related pulmonary toxicity has been observed. Conclusions: AZD0530 can be administered safely as a single agent in patients with a variety of advanced STS. To date, tumor responses have not been noted; however patients were not selected based on tumor target expression. Further testing may be warranted in selected tumors in combination with chemotherapy given pre-clinical synergy data or in tumors pre-selected for target expression. No significant financial relationships to disclose.
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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 | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".