{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:04:47Z","timestamp":1780668287868,"version":"3.54.1"},"reference-count":47,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Medical Science and Technology Research Project","award":["LHGJ20210172"],"award-info":[{"award-number":["LHGJ20210172"]}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["242300420091"],"award-info":[{"award-number":["242300420091"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technique Foundation of Henan Province","award":["222102310424"],"award-info":[{"award-number":["222102310424"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,8,11]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Systemic therapies for advanced gastric cancer (GC), including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has become the standard first-line (1L) treatment for advanced gastric or gastro-oesophageal junction (G\/GEJ) cancer, although there remains a need for improvement in efficacy. Fruquintinib, an oral and highly selective vascular endothelial growth factor receptor inhibitor, has shown a synergistic antitumour effect when paired with ICI or chemotherapy. Moreover, it has demonstrated a tolerable safety profile and high potential for synergy with chemotherapy or immunotherapy, suggesting that a combination of fruquintinib, sintilimab and oxaliplatin+capecitabine (CAPEOX) can be a promising treatment for locally advanced G\/GEJ cancer. This phase 1b\/2 study aims to investigate the safety and efficacy of the combination of fruquintinib, sintilimab and CAPEOX regimen as a 1L combination therapy for unresectable advanced or metastatic G\/GEJ cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The FUNCTION trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06329973\">NCT06329973<\/jats:ext-link>\n                      ) is a single-arm, prospective, multicentre, phase Ib\/II clinical trial that will consist of a dose escalation phase and an expansion phase. The study is planned to be conducted at 16 public hospitals. A total of 70 participants will be enrolled, comprising nine in the dose escalation phase and 61 in the expansion phase. The dosing regimen during the dose escalation phase will include three different doses of fruquintinib (3 mg, 4 mg and 5\u2009mg, per oral, once per day days 1\u201314) + sintilimab, 200\u2009mg, intravenous, day 1 +oxaliplatin 130 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , day 1, intravenous, + capecitabine 800 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , per oral, twice daily, days 1\u201314, every 21 days. The recommended phase 2 dose (RP2D) and maximum tolerated dose will be determined in the escalation phase, and the RP2D will be used in the expansion phase. The primary endpoints will be the maximum tolerated dose and objective response rate; the secondary endpoints will include OS, progression-free survival, disease control rate, duration of response, surgical conversion rate and adverse events and identification of molecular biomarkers for efficacy. The results from this study will provide evidence for expanding the clinical applications of fruquintinib plus sintilimab and CAPEOX as a 1L combination therapy in metastatic or non-resectable, locally advanced G\/GEJ cancer and lay the foundation for future large-scale clinical investigations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will be conducted in full compliance with the ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH) GCP (Good Clinical Practice, GCP) guidelines, the rules of the Declaration of Helsinki and ICH E2A (Clinical Safety Data Management: Definitions and Standards for Expedited Reporting) Guidelines . The study protocol has received approval from the Henan Cancer Hospital ethical committee (Approval No. 2023-237-002). Written informed consent will be obtained from all patients prior to enrolment. For patients who have the mental capacity for informed consent, their consent for participation will be sought and will not be overridden by their family members. For patients who have impaired cognition, informed consent will be sought from their legally acceptable representative. On completion of the analyses, the study findings will be disseminated locally and internationally through manuscript publications in peer-reviewed journals and conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06329973\">NCT06329973<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-100241","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T09:02:12Z","timestamp":1758877332000},"page":"e100241","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Single-arm, open-label, multicentre phase 1b\/2 study to evaluate the safety and efficacy of fruquintinib combined with sintilimab and CAPEOX as a first-line treatment for advanced gastric or gastroesophageal junction adenocarcinoma (FUNCTION study): a study protocol"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06329973","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06329973","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06329973","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Beibei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, 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