A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC)

Abstract

Background Immunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic relapsed ovarian cancer. Objective To assess the effectiveness and safety of MVA-5T4 as treatment for asymptomatic relapsed ovarian cancer. Methods TRIOC was a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aim was to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. Eligible patients had International Federation of Gynecology and Obstetrics (FIGO) stage IC1–III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, Eastern Cooperative Oncology Group (ECOG) 0–1, with relapse defined by a rise in CA-125 to twice the upper limit of normal or low-volume disease on CT scan. The primary endpoint was disease progression (including deaths from ovarian cancer) at 25 weeks. Following a brief suspension, the trial restarted as a single-arm study. The revised single-arm design required 45 evaluable patients treated with MVA-5T4 to detect a 25-week progression rate of 50%, assuming an expected 70% rate without MVA-5T4; 85% power with one-sided 5% significance. Results A total of 94 eligible patients were recruited, median age was 65 years (range 42–82), median follow-up 34 months (range 2–46). Overall, 59 patients received MVA-5T4 and 35 patients received placebo. The median number of MVA-5T4 injections received was 7 (range 0–9), compared with a median of 6 (range 1–12) for patients receiving placebo. Median progression-free survival was the same in both arms (3.0 months). The 25-week progression rate was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference −5.7%, 95% CI −21.4% to 10.0%). Median time to clinical intervention was improved with MVA-5T4: 7.6 months (range 6.7–9.5) vs 5.6 (range 4.9–7.6), Conclusion MVA-5T4 vaccination in patients with asymptomatic relapse was well-tolerated but did not improve the progression rate at 25 weeks. The majority of patients who received MVA-5T4 had clinical intervention later than those assigned to placebo. Trial registration number NCT01556841 .