A Phase Ii Clinical Trial Platform For Sensitization Testing Using Total Neoadjuvant Therapy (Tnt) In Rectal Cancer: Nrg-Gi002.

TPS721Background: Locally advanced rectal cancer (LARC) improvements have plateaued due to an inability to consistently deliver adjuvant therapy and effective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers is needed to advance treatment outcomes. This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EA) in LARC. The EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk patient (pt) population with correlative biomarkers. Success of any EA will be determined by achievement of pathologic endpoints compared to a control arm. Methods: The NRG-GI002 trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC with any ONE of the following: distal location (cT3-4 ≤ 5 cm from anal verge, any N); bulky (any cT4 or tumor within 3 m...