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Primary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: OVHIPEC-2, a phase III randomized clinical trial
  1. Simone Koole1,2,
  2. Ruby van Stein1,2,
  3. Karolina Sikorska3,
  4. Desmond Barton4,
  5. Lewis Perrin5,
  6. Donal Brennan6,
  7. Oliver Zivanovic7,
  8. Berit Jul Mosgaard8,
  9. Anna Fagotti9,
  10. Pierre-Emmanuel Colombo10,
  11. Gabe Sonke2 and
  12. W J van Driel1,11,12,13
  13. on behalf of the OVHIPEC-2 Steering Committee and the Dutch OVHIPEC group
    1. 1 Department of Gynaecology, Netherlands Cancer Institute, Amsterdam, The Netherlands
    2. 2 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
    3. 3 Department of Biostatistics, Netherlands Cancer Institute, Amsterdam, Noord-Holland, The Netherlands
    4. 4 Department of Gynaecological Oncology, Royal Marsden Hospital NHS Trust, London, UK
    5. 5 Queensland Centre for Gynaecological Cancer, Herston, Queensland, Australia
    6. 6 Gynaecology Oncology, Mater Misericordiae University Hospital, Dublin, Ireland
    7. 7 Department of Gynecologic Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    8. 8 Department of Gynaecology, Copenhagen University Hospital, Copenhagen, Denmark
    9. 9 Dipartimento Scienze della Salute della Donna e del Bambino, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy
    10. 10 Department of Surgical Oncology, Institut régional du Cancer de Montpellier, Montpellier, France
    11. 11 Center for Gynaecologic Oncology Amsterdam, Center for Gynaecologic Oncology Amsterdam, Amsterdam, The Netherlands
    12. 12 Dutch Gynecological Oncology Group (DGOG), the Netherlands, the Netherlands
    13. 13 Dutch Peritoneal Oncology Group (DPOG), the Netherlands, the Netherlands
    1. Correspondence to Dr W J van Driel, Department of Gynaecology, Netherlands Cancer Institute, Amsterdam, Noord-Holland 1066 CX, The Netherlands; w.v.driel{at}nki.nl

    Abstract

    Background The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery. The effect of HIPEC remains undetermined in patients who are candidates for primary cytoreductive surgery.

    Primary objective The primary objective is to evaluate the effect of HIPEC on overall survival in patients with FIGO stage III epithelial ovarian cancer who are treated with primary cytoreductive surgery resulting in no residual disease, or residual disease up to 2.5 mm in maximum dimension.

    Study hypothesis We hypothesize that the addition of HIPEC to primary cytoreductive surgery improves overall survival in patients with primary FIGO stage III epithelial ovarian cancer.

    Trial design This international, randomized, open-label, phase III trial will enroll 538 patients with newly diagnosed FIGO stage III epithelial ovarian cancer. Following complete or near-complete (residual disease ≤2.5 mm) primary cytoreduction, patients are randomly allocated (1:1) to receive HIPEC or no HIPEC. All patients will receive six courses of platinum-paclitaxel chemotherapy, and maintenance PARP-inhibitor or bevacizumab according to current guidelines.

    Major eligibility criteria Patients with FIGO stage III primary epithelial ovarian, fallopian tube, or primary peritoneal cancer are eligible after complete or near-complete primary cytoreductive surgery. Patients with resectable umbilical, spleen, or local bowel lesions may be included. Enlarged extra-abdominal lymph nodes should be negative on FDG-PET or fine-needle aspiration/biopsy.

    Primary endpoint The primary endpoint is overall survival.

    Sample size To detect a HR of 0.67 in favor of HIPEC, 200 overall survival events are required. With an expected accrual period of 60 months and 12 months additional follow-up, 538 patients need to be randomized.

    Estimated dates for completing accrual and presenting results The OVHIPEC-2 trial started in January 2020 and primary analyses are anticipated in 2026.

    Trial registration ClinicalTrials.gov:NCT03772028

    • ovarian cancer
    • surgical oncology
    • peritoneal neoplasms
    • surgical procedures, operative
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    Footnotes

    • Twitter @hetAVL

    • Collaborators The International OVHIPEC-2 Steering Committee (in alphabetical order): N Bakrin, S Banerjee, S Barry, DP Barton, D Brennan, PE Colombo, M Deraco, WJ van Driel, A Fagotti, R Farrell, R Grisham, BJ Mosgaard, I McNeish, L Perrin, GS Sonke, O Zivanovic. The Dutch OVHIPEC group (in alphabetical order): HJG Arts, I Boere, GJ Creemers, WJ van Driel, KN Gaarenstroom, M van Gent, M van Ham, B Hellebrekers, R Hermans, I de Hingh, SN Koole, JR Kroep, CD de Kroon, R Lalisang, S Lambrechts, P Ottevanger, N Reesink, V Retel, AKL Reyners, EM Roes, HWR Schreuder, GS Sonke, RM van Stein, A Thijs, A Westermann, PO Witteveen, A Wymenga, R Yigit. Dutch Gynaecological Oncology Group (DGOG), Dutch Peritoneal Oncology Group (DPOG).

    • Contributors Conception and study design: WJvD, GS, SK, RvS, OVHIPEC-2 Steering Committee, Dutch OVHIPEC group. Statistical calculations: KS. Manuscript writing: SK, WJvD, GS. Manuscript editing and reviewing: RvS, KS, DB, LP, DB, OZ, BJM, AF, PE-C, GS, WJvD. Final approval of manuscript: SK, WJvD, GS.

    • Funding The trial is funded by the Dutch Cancer Society (DCS), the Netherlands Organization for Health Research and Development (ZonMW), and the Coverage with Evidence Development (CED) program of the Dutch Ministry of Health.

    • Competing interests None declared.

    • Patient consent for publication Not required.

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

    • Data availability statement Data will be available upon request

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