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.

Authors

Thomas George

Thomas J. George

NRG Oncology, and The University of Florida Health Cancer Center, Gainesville, FL

Thomas J. George , Greg Yothers , Theodore S. Hong , Marcia McGory Russell , Y. Nancy You , William Parker , Samuel A. Jacobs , Peter C. Lucas , Marc Jeffrey Gollub , William Adrian Hall , Lisa A. Kachnic , Namrata Vijayvergia , Norman Wolmark

Organizations

NRG Oncology, and The University of Florida Health Cancer Center, Gainesville, FL, NRG Oncology, and The University of Pittsburgh, Pittsburgh, PA, NRG Oncology and Massachusetts General Hospital, Boston, MA, NRG Oncology, and The VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, Los Angeles, CA, NRG Oncology, and The University of Texas MD Anderson Cancer Center, Houston, TX, NRG Oncology, and McGill University Health Centre, Montreal, QC, Canada, NRG Oncology,and The University of Pittsburgh Cancer Institute, Pittsburgh, PA, NRG Oncology, and University of Pittsburgh School of Medicine, Pittsburgh, PA, NRG Oncology, and Memorial Sloan Kettering Cancer Center, New York, NY, Medical College of Wisconsin, Milwaukee, WI, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, NRG Oncology, and Fox Chase Cancer Center/ECOG-ACRIN, Philadelphia, PA, NRG Oncology, and The Allegheny Health Network Cancer Institute, Pittsburgh, PA

Research Funding

U.S. National Institutes of Health
Pharmaceutical/Biotech Company

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

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Gastrointestinal (Colorectal) Cancer

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer–Local-Regional Disease

Clinical Trial Registration Number

NCT02921256

Citation

J Clin Oncol 37, 2019 (suppl; abstr 3505)

DOI

10.1200/JCO.2019.37.15_suppl.3505

Abstract #

3505

Abstract Disclosures

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