MORPHEUS Phase II–III Study: A Pre-Planned Interim Safety Analysis and Preliminary Results

Background: We explored image-guided adaptive endorectal brachytherapy patients electing non-operative management for rectal cancer. We present the first pre-planned interim analysis. Methods: In this open-label phase II–III randomized study, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with 5-FU/Capecitabine. They were randomized 1:1 to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A) or three weekly adaptive brachytherapy (IGAEBT) boosts totaling 30 Gy (Arm B). Patient characteristics and toxicity are presented using descriptive analyses; TME-free survival between arms with the intention to treat the population is explored using the Kaplan–Meier method. Results: A total of 40 patients were in this analysis. Baseline characteristics were balanced; acute toxicities were similar. Complete clinical response (cCR) was 50% (n = 10/20) in Arm A and 90% in Arm B (n = 18/20). Median follow-up was 1.3 years; 2-year TME-free survival was 38.6% (95% CI: 16.5–60.6%) in the EBRT arm and 76.6% (95% CI: 56.1–97.1%) in the IGAEBT arm. Conclusions: Radiation intensification with IGAEBT is feasible. This interim analysis suggests an improvement in TME-free survival when comparing IGAEBT with EBRT, pending confirmation upon completion of this trial.