Phase II open-label randomized multi-centre study of neoadjuvant olaparib in patients (pts) with platinum sensitive (PS) relapsed high grade serous ovarian cancer (OC): The NEO trial.
Bibliographic record
Abstract
TPS5608 Background: Olaparib is a PARP inhibitor with clinical benefit in relapsed OC, especially in pts with germline BRCA1/2 mutation ( gBRCA). Study 19 (NCT00753545) found a progression free survival (PFS) gain from maintenance olaparib, post chemotherapy for PS relapse. Olaparib treatment in gBRCA OC pts relapsing post ≥ 3 prior chemotherapy regimens gave a response rate (RR) of 46% in the PS subgroup (Study 42; NCT01078662). Efficacy of olaparib may extend to OC with homologous recombination DNA repair pathway deficiency (HRD); susceptible to synthetic lethality from PARP inhibition. NEO [NCT02489006] is a window of opportunity study to assess tumor heterogeneity and the pharmacodynamic effects of olaparib given prior to surgery in PS OC, analyse the tumor genomic landscape pre and post olaparib, and assess for predictive biomarkers beyond BRCA mutation. Methods: This phase 2 study enrols pts with high grade serous OC, primary peritoneal or fallopian tube cancer with a progression free interval of ≥6 months and sensitive to their last line of platinum therapy. Pts must be suitable for secondary debulking surgery and agree to pre-operative tumour biopsy. All pts receive olaparib tablets 300mg po bid for 6 ± 2 weeks pre-surgery. Post-operatively, pts are randomised 1:1 to olaparib or 6 cycles of platinum-based chemotherapy followed by maintenance olaparib. The primary endpoint is the degree of PAR and PARP-1 inhibition in the blood and tumor following pre-operative olaparib in PS relapsed OC. Clinical efficacy is assessed by RR (RECIST 1.1), CA125, PFS and PFS2. Translational studies include next generation sequencing HRD panel to assess for somatic and germline mutations including RAD51B/C/D, PPM1D, FANCM, BRIP1, PALB2 and BARD1; evaluation of gene expression change in tumor tissue pre and post olaparib; assessment for resistance mechanisms and impact of heterogeneity. Circulating tumor DNA measured weekly pre-surgery is assessed for its prognostic value, alone and compared with CA125. The study will enrol 50-70 pts with estimated accrual of 3 pts/month across multiple sites, and opened at Princess Margaret Cancer Centre in 7/2016. Clinical trial information: NCT02489006.
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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 | 0.001 |
| 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 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 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".