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A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC)
  1. Agnieszka Michael1,
  2. William Wilson2,
  3. Sunny Sunshine1,
  4. Nicola Annels1,
  5. Richard Harrop3,
  6. Daniel Blount4,
  7. Hardev Pandha1,
  8. Rosemary Lord5,
  9. Yen Ngai2,
  10. Shibani Nicum6,
  11. Laura Stylianou2,
  12. Stephen Gwyther7,
  13. Iain A McNeish8,
  14. Allan Hackshaw9 and
  15. Jonathan Ledermann9
    1. 1Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK
    2. 2Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK
    3. 3Oxular, Oxford, Oxfordshire, UK
    4. 4Barinthus Biotherapeutics (UK) Ltd, Oxford, Oxfordshire, UK
    5. 5Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK
    6. 6University College London, London, UK
    7. 7Surrey and Sussex NHS Healthcare Trust, Redhill, UK
    8. 8Department of Surgery and Cancer, Imperial College London, London, UK
    9. 9UCL Cancer Institute, University College London, UK
    1. Correspondence to Professor Agnieszka Michael, Department of Clinical and Experimental Medicine, University of Surrey, Guildford W1T 4TJ, UK; A.Michael{at}surrey.ac.uk

    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.

    • Carcinoma, Ovarian Epithelial

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • X @AgnMichael

    • Contributors AM: chief investigator for the study, overall study guarantor, study design and grant submission, oversight of recruitment, data analysis, manuscript writing. WW and AH: statistical study design, data analysis, manuscript writing, data oversight. SS, NA, and HP: immunological and translational analysis and writing support. RH, DB: Oxford Biomedica study development support, immunological and translational analysis of samples. RL, SN, SG, and IAM: patient recruitment, study design support, data analysis support, manuscript writing support. LS and YN: project manager, patients’ recruitment oversight, study conduct support, data analysis support, manuscript writing support. JL: overall study design and conduct oversight on behalf of the study sponsor.

    • Funding The TRIOC trial was funded by Oxford Biomedica who supplied the MVA-5T4 (TroVax) and placebo as well as providing funding for trial-associated costs. Cancer Research UK provided endorsement for the trial (grant reference C34426/A15045).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.