TUXEDO: a phase I/II trial of cetuximab with chemoradiotherapy in muscle-invasive bladder cancer

Objective: To assess the feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle-invasive bladder cancer. Patients and Methods: TUXEDO was a prospective, single-arm, open-label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400 mg/m2 on Day 1 of Week −1, and then seven weekly doses of 250 mg/m2. The radiotherapy schedule was 64 Gy/32F with Day 1 mitomycin C (12 g/m2) and 5-fluorouracil (500 mg/m2/day) over Days 1–5 and Days 22–26. Patients with T2-4aN0M0 urothelial cancer and a performance status of 0–1 were eligible. Prior neoadjuvant therapy was permitted. The Phase I primary outcome was impact on radiotherapy treatment completion and toxicity experienced during treatment. The Phase II primary outcome was local control at 3 months post treatment. Results: Between September 2012 and October 2016, 33 patients were recruited; seven in Phase I, 26 in Phase II. Three patients in Phase II were subsequently deemed ineligible and received no trial therapy. Eight patients discontinued cetuximab due to adverse effects. The patients’ median (range) age was 70.1 (60.6–75.1) years, 20 had a performance status of 0, 27 were male and 26 had already received neoadjuvant chemotherapy. In Phase I, all patients completed planned radiotherapy, with no delays or dose reductions. Of the 30 evaluable patients in Phase II, 25 had confirmed local control 3 months after treatment (77%, 95% confidence interval 58–90). During the trial there were 18 serious adverse events. The study was halted due to slow accrual. Conclusion: Phase I data demonstrate it is feasible and safe to add cetuximab to chemoradiotherapy. Exploratory analysis of Phase II data provides evidence to consider further clinical evaluation of cetuximab in this setting