Phase II study of PX-866 in recurrent glioblastoma.
Bibliographic record
Abstract
2053 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: A multinomial design of response and early progression (< 8 weeks on study) was used. In stage 1 (15 pts), 0 responses and ≥ 10 early progressions would stop accrual; after full accrual, ≥ 4 responses OR ≤ 13 early progressions was prespecified as of interest. Pts with histologically confirmed GBM, at first recurrence after chemoradiation and adjuvant temozolomide were given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam were done every cycle (8 weeks). Tumour tissue was collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRviii, PIK3CA mutations). Results: A total of 33 pts were enrolled, eligible and evaluable. Median age was 56 (range 35-78), 12 were female; 29 had performance status (PS) 0-1 and 4 had PS 2. Median time from initial diagnosis to enrolment was 308 days (range 141-1256). Median number of cycles was 1 (range 1-7). Thirty-two pts have discontinued therapy, 26 due to disease/symptomatic progression and 6 due to toxicity (5 LFT elevation and 1 allergic reaction). Other adverse effects (AE): fatigue (16 pts/2 grade 3), diarrhea (11 pts/5 grade 3), nausea (19 pts/1 grade 3), vomiting (11 pts/1 grade 3) and lymphopenia (29 pts/7 grade 3/4). Five pts had related serious AEs (1 LFTs, 1 GI and 3 venous thromboembolism) All pts were evaluable for response; 25 had a best response of progression, 1 had partial response (overall response rate 3%) and seven (21%) had stable disease (SD, median 7.3 months; range 3.1-13.6). Six month PFS was 17%. In preliminary analyses, no statistical association was found between SD and PTEN or EGFRviii status (results pending in 16 pts). Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of pts obtained durable stable disease. Further correlative work is required to identify the predictor of this effect. Clinical trial information: NCT01259869.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".