2133 - A Phase II Trial of the Efficacy and Safety of Short Course Radiation Therapy and Long Course Chemo-Radiation Therapy with and without Radioprotector as Part of Total Neoadjuvant Therapy in Locally Advanced Rectal Adenocarcinoma
Presenter(s)
C. Lin1, and R. E. Oberley-Deegan2; 1Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE, 2Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE
Purpose/Objective(s): We previously completed a Phase I/II trial in patients with newly diagnosed anal squamous cell carcinoma treated with concurrent radiation therapy, 5-fluorouracil, mitomycin, and an investigational redox-active manganese porphyrin radioprotective agent, which demonstrated reduced grade =3 gastrointestinal and skin toxicities. Building on these results, we initiated this NIH-sponsored, multi-institutional Phase II trial in rectal adenocarcinoma, as acute gastrointestinal, genitourinary, and skin toxicities remain common during total neoadjuvant therapy (TNT) for locally advanced rectal adenocarcinoma (LARC), potentially impacting treatment tolerance and quality of life. This study evaluates whether this investigational radioprotective agent reduces acute normal tissue toxicity when combined with short-course radiotherapy (SCRT) or long-course chemoradiotherapy (LCCRT) as part of TNT in patients with newly diagnosed LARC. Correlative studies include blood and urine biomarkers of chemoradiation injury and post-surgical tumor and adjacent normal tissue analyses.
Materials/Methods: This is a multi-cohort, randomized Phase II trial in patients with LARC eligible for TNT with consolidative chemotherapy. Patients are assigned to SCRT or LCCRT prior to randomization. Cohort 1 (LCCRT) included a completed 6-patient safety lead-in of the investigational radioprotective agent with capecitabine-based chemoradiotherapy; no dose-limiting toxicities were observed, and the randomized phase is ongoing. Cohort 2 (SCRT) randomizes patients to SCRT with or without the investigational radioprotective agent. Within each cohort, patients are randomized (stratified by gender) to the investigational radioprotective agent or no radioprotective agent. Following RT, patients receive consolidation chemotherapy (9 cycles FOLFOX or 6 cycles CAPOX). Patients achieving clinical complete response may undergo watch-and-wait management. Acute skin, GI, and GU toxicities and patient-reported quality of life are assessed longitudinally. Secondary endpoints include postoperative complications, late toxicity, pathologic response, local control, locoregional DFS, and OS. The trial is actively accruing at three institutions. Clinical trial registry number: NCT05254327.
Results: TBD
Conclusion: TBD