ARTIA-Cervix: A Prospective Clinical Trial to Assess Patient Reported Intestinal Toxicity with Adaptive External Beam Radiation Therapy in the Treatment of Cervical Cancer

Abstract

Chemoradiation (CRT) remains the standard of care for locally advanced cervical cancer. As recent large phase III trials (OUTBACK, CALLA) reported no difference in primary survival outcomes when novel agents were added to CRT, technological advancements continue to be a focus for improving outcomes. Daily imaging has enabled margin reduction on the cervix, uterus and lymph nodes, which can lower radiation dose to bowel and potentially reduce RT-related symptoms. Daily adaptive RT (ART) combines daily imaging with online dosimetry replanning, allowing for decreased margins on the target. A pre-planning study showed bowel V40Gy and V45Gy reductions of 252 cc to140 cc and 167 cc to 43 cc, respectively. ARTIA-Cervix is a single-arm, prospective, multi-institutional, international clinical trial investigating the potential of ART to decrease patient-reported acute gastrointestinal (GI) toxicity. Planned enrollment is 125 subjects with up to 8 sites participating. Eligibility criteria include locally advanced node-negative cervical cancer FIGO stages IB2-3B. Treatment will consist of cisplatin-based CRT with daily ART, followed by image-guided brachytherapy. Subjects will receive 25 fractions ART at 1.8 Gy per day for a total of 45 Gy. The primary study objective is reduction of patient-reported GI toxicity as measured by PRO-CTCAE score ≥3 at the conclusion of ART. Secondary objectives include patient-reported GU toxicity and sexual quality of life, the development of radiation dosimetry models predicting toxicity, physician-reported toxicities, 2-year disease free survival, and adaptive workflow metrics. Powering of the study and sample size calculation are based on the hypothesis that ART will decrease patient-reported acute GI toxicity from historical rates of 33% to 20% (13% effect size). This study opened to enrollment on April 28th, 2022. The total study duration will be approximately 5 years. ARTIA-Cervix is an international, prospective clinical trial designed to evaluate reduction of treatment-related GI toxicity through daily online ART. The results of this clinical study will add to the growing body of evidence supporting clinical decisions about utilization of ART technologies.