NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC)—First experimental arm (EA) initial results.
Bibliographic record
Abstract
3505 Background: This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel EAs in LARC. EAs are not intended for direct comparison, but rather to test a variety of hypotheses in a consistent high-risk pt population with correlative biomarkers. Primary endpoint (EP) and available secondary EPs from the first EA using veliparib (a PARPi) are reported. NCT02921256. Methods: Stage II/III pts with LARC (with any ONE of the following: distal location [cT3-4 ≤5cm from anal verge, any N]; bulky [any cT4 or tumor within 3mm of mesorectal fascia]; high risk for metastatic disease [cN2]; or not a sphincter-sparing surgery [SSS] candidate) were randomized to neoadjuvant FOLFOX (x 4mo) → chemoRT (cape with 50.4Gy +/- veliparib 400mg PO BID) → surgery 8-12 wks later. Primary EP: 4 point reduction in Neoadjuvant Rectal Cancer (NAR) score with a one-sided α = 0.10 and 80% power. NAR compared by linear model controlling for stratification and possibly other factors. Secondary EPs: OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, and SSS. Binary EPs compared by Fisher’s exact test. Reported p-values are two-sided. Results: From 10/2016 - 2/2018, 178 pts were randomized (88 control, 90 veliparib). Baseline characteristics were balanced except for candidate for SSS at entry (39% control, 61% veliparib). 140 pts were evaluable for NAR (72 control, 68 veliparib). Mean NAR was 12.6 control (95% CI: 9.8–15.3) vs 13.7 for veliparib (CI: 10.2–17.2). Controlling for stratification (p = 0.69) or stratification and candidate for SSS (p = 0.78), NAR difference was not significant. pCR = 21.6% vs 33.8% (p = 0.14); cCR = 28.2% vs 33.3% (p = 0.60); and SSS = 52.5% vs 59.3% (p = 0.43). Most common grade 3/4 AEs were diarrhea and cytopenias. The EA had two deaths (cardiac arrest [FOLFOX]; enterocolitis [chemoRT]). Conclusions: Veliparib added to chemoRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. Support: U10CA180868, -180822; UG1-189867; U24-196067; AbbVie. Clinical trial information: NCT02921256.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.010 | 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".