CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer
Astrid E. Slagter,
Edwin P. M. Jansen,
Hanneke W. M. van Laarhoven,
Johanna W. van Sandick,
Nicole C. T. van Grieken,
Karolina Sikorska,
Annemieke Cats,
Pietje Muller-Timmermans,
Maarten C. C. M. Hulshof,
Henk Boot,
Maartje Los,
Laurens V. Beerepoot,
Frank P. J. Peters,
Geke A. P. Hospers,
Boudewijn van Etten,
Henk H. Hartgrink,
Mark I. van Berge Henegouwen,
Grard A. P. Nieuwenhuijzen,
Richard van Hillegersberg,
Donald L. van der Peet,
Heike I. Grabsch,
Marcel Verheij
Affiliations
Astrid E. Slagter
Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Edwin P. M. Jansen
Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Hanneke W. M. van Laarhoven
Department of Medical Oncology, Academic Medical Center Amsterdam
Johanna W. van Sandick
Department of Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Nicole C. T. van Grieken
Department of Pathology, VU University Medical Center
Karolina Sikorska
Statistical Department, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Annemieke Cats
Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Pietje Muller-Timmermans
Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Maarten C. C. M. Hulshof
Department of Radiation Oncology, Academic Medical Center Amsterdam
Henk Boot
Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Maartje Los
Department of Medical Oncology, St. Antonius Hospital
Laurens V. Beerepoot
Department of Medical Oncology, St. Elisabeth Hospital
Frank P. J. Peters
Department of Medical Oncology, Zuyderland Sittard-Geleen
Geke A. P. Hospers
Department of Medical Oncology, University Medical Center Groningen
Boudewijn van Etten
Department of Surgery, University Medical Center Groningen
Henk H. Hartgrink
Department of Surgery, Leiden University Medical Center
Mark I. van Berge Henegouwen
Department of Surgery, Academic Medical Center Amsterdam
Grard A. P. Nieuwenhuijzen
Department of Surgery, Catharina Hospital Eindhoven
Richard van Hillegersberg
Department of Surgery, University Medical Center Utrecht
Donald L. van der Peet
Department of Surgery, VU University Medical Center
Heike I. Grabsch
Department of Pathology, GROW – School for Oncology and Developmental Biology, Maastricht University Medical Center
Marcel Verheij
Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek
Abstract Background Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy. Methods In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers. Discussion The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial. Trial registration clinicaltrials.gov NCT02931890; registered 13 October 2016. Date of first enrolment: 21 December 2017.