Study of Chemoradiation Adjusted by HPV ctDNA Levels With or Without Retifanlimab in Advanced Anal Cancer

What this Trial Is About

Researchers are evaluating how to customize chemoradiation therapy CRT doses for people with locally advanced anal cancer, focusing on tailoring treatment based on tumor response measured by HPV circulating tumor DNA ctDNA. The study aims to find out if adjusting the dose of chemotherapy and radiation using this blood test can improve survival and reduce side effects. Some participants whose cancer does not respond well may receive an additional immune-stimulating drug called Retifanlimab. Participants will first receive one cycle of CRT over 4 weeks while undergoing HPV ctDNA testing. Based on their ctDNA response, the dose of CRT will be adjusted those with a favorable response will have a reduced radiation dose, those with an intermediate response will receive the standard dose, and those with an unfavorable response will have an increased radiation dose followed by Retifanlimab infusions for up to one year. Chemotherapy includes Mitomycin-C and either Capecitabine or 5-Fluorouracil. During the study, participants will undergo regular blood tests to monitor HPV ctDNA and other assessments including scans and physical exams. Researchers will measure disease-free survival at 1 and 2 years, disease control, toxicity, and patient-reported outcomes related to fecal incontinence and sexual function. The study lasts until January 2029, with ongoing evaluations to assess the safety and impact of personalized CRT dosing and Retifanlimab treatment.

ctHPVDNA Response-Adapted Chemoradiation +/- Retifanlimab Treatment in Locally-Advanced Anal Cancer