Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial
BackgroundLocally advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma faces high recurrence risks despite radical surgery. Perioperative chemotherapy (e.g., FLOT regimen) improves survival but has limited pathological complete response (pCR) rates and significant toxicity. Immunotherap...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638316/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850075301722193920 |
|---|---|
| author | Xiangyu Meng Dong Yang Yuanlin Liu Chao Wang Junqiao Yao Tao Zhang |
| author_facet | Xiangyu Meng Dong Yang Yuanlin Liu Chao Wang Junqiao Yao Tao Zhang |
| author_sort | Xiangyu Meng |
| collection | DOAJ |
| description | BackgroundLocally advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma faces high recurrence risks despite radical surgery. Perioperative chemotherapy (e.g., FLOT regimen) improves survival but has limited pathological complete response (pCR) rates and significant toxicity. Immunotherapy and anti-angiogenic agents show promise in advanced G/GEJ cancer. This trial evaluates fruquintinib (a VEGFR-1/2/3 inhibitor), sintilimab (PD-1 inhibitor), and SOX (oxaliplatin+S-1) as perioperative therapy for resectable locally advanced G/GEJ adenocarcinoma.MethodsThis prospective, single-arm, phase II trial (N = 25) enrolls treatment-naïve adults (18–75 years) with histologically confirmed, resectable cT3-4aN+M0 G/GEJ adenocarcinoma (AJCC 8th edition). Patients receive 3 cycles of neoadjuvant therapy:Fruquintinib:4 mg orally, days 1–14 (21-day cycle). S-1: 80–120 mg orally twice daily (based on BSA), days 1–14. Oxaliplatin: 130 mg/m² IV, day 1. Sintilimab: 200 mg IV, day 1.Radical gastrectomy with D2 lymphadenectomy follows 4–6 weeks post-neoadjuvant therapy. Adjuvant therapy (3 cycles of sintilimab for pCR patients; 3 cycles of preoperative regimen for non-pCR) starts 4–6 weeks post-surgery. Endpoints: Primary: pCR rate (ypT0/Tis ypN0 per CAP criteria). Secondary: R0 resection rate, major pathological response (MPR, ≤10% residual tumor), 2-year event-free survival (EFS), 2-year overall survival (OS), safety (NCI CTCAE v5.0). Exploratory: Biomarker analysis of tumor microenvironment. Statistical Analysis: Sample size (25 patients) was calculated using Fisher’s exact test (one-sided α = 0.05, power = 80%), assuming pCR improvement from 5% (historical control) to 20%. Efficacy analyses use intention-to-treat (ITT) population; safety analyses include patients receiving ≥1 neoadjuvant dose.DiscussionThis is the first trial combining fruquintinib, sintilimab, and SOX in perioperative G/GEJ cancer. If successful, it may expand treatment options for locally advanced disease. Limitations include single-arm design and small sample size.Trial RegistrationChinese Clinical Trial Registry (ChiCTR2400084194) |
| format | Article |
| id | doaj-art-95b9deb03e6049598d47eaeac027f3b7 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-95b9deb03e6049598d47eaeac027f3b72025-08-20T02:46:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16383161638316Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trialXiangyu MengDong YangYuanlin LiuChao WangJunqiao YaoTao ZhangBackgroundLocally advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma faces high recurrence risks despite radical surgery. Perioperative chemotherapy (e.g., FLOT regimen) improves survival but has limited pathological complete response (pCR) rates and significant toxicity. Immunotherapy and anti-angiogenic agents show promise in advanced G/GEJ cancer. This trial evaluates fruquintinib (a VEGFR-1/2/3 inhibitor), sintilimab (PD-1 inhibitor), and SOX (oxaliplatin+S-1) as perioperative therapy for resectable locally advanced G/GEJ adenocarcinoma.MethodsThis prospective, single-arm, phase II trial (N = 25) enrolls treatment-naïve adults (18–75 years) with histologically confirmed, resectable cT3-4aN+M0 G/GEJ adenocarcinoma (AJCC 8th edition). Patients receive 3 cycles of neoadjuvant therapy:Fruquintinib:4 mg orally, days 1–14 (21-day cycle). S-1: 80–120 mg orally twice daily (based on BSA), days 1–14. Oxaliplatin: 130 mg/m² IV, day 1. Sintilimab: 200 mg IV, day 1.Radical gastrectomy with D2 lymphadenectomy follows 4–6 weeks post-neoadjuvant therapy. Adjuvant therapy (3 cycles of sintilimab for pCR patients; 3 cycles of preoperative regimen for non-pCR) starts 4–6 weeks post-surgery. Endpoints: Primary: pCR rate (ypT0/Tis ypN0 per CAP criteria). Secondary: R0 resection rate, major pathological response (MPR, ≤10% residual tumor), 2-year event-free survival (EFS), 2-year overall survival (OS), safety (NCI CTCAE v5.0). Exploratory: Biomarker analysis of tumor microenvironment. Statistical Analysis: Sample size (25 patients) was calculated using Fisher’s exact test (one-sided α = 0.05, power = 80%), assuming pCR improvement from 5% (historical control) to 20%. Efficacy analyses use intention-to-treat (ITT) population; safety analyses include patients receiving ≥1 neoadjuvant dose.DiscussionThis is the first trial combining fruquintinib, sintilimab, and SOX in perioperative G/GEJ cancer. If successful, it may expand treatment options for locally advanced disease. Limitations include single-arm design and small sample size.Trial RegistrationChinese Clinical Trial Registry (ChiCTR2400084194)https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638316/fullG/GEJ adenocarcinomaperioperative treatmentfruquintinibsintilimabeffectiveness |
| spellingShingle | Xiangyu Meng Dong Yang Yuanlin Liu Chao Wang Junqiao Yao Tao Zhang Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial Frontiers in Immunology G/GEJ adenocarcinoma perioperative treatment fruquintinib sintilimab effectiveness |
| title | Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial |
| title_full | Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial |
| title_fullStr | Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial |
| title_full_unstemmed | Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial |
| title_short | Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase II clinical trial |
| title_sort | fruquintinib and sintilimab plus sox as perioperative therapy for locally resectable advanced gastric gastroesophageal junction adenocarcinoma study protocol for a prospective single arm phase ii clinical trial |
| topic | G/GEJ adenocarcinoma perioperative treatment fruquintinib sintilimab effectiveness |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1638316/full |
| work_keys_str_mv | AT xiangyumeng fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial AT dongyang fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial AT yuanlinliu fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial AT chaowang fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial AT junqiaoyao fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial AT taozhang fruquintinibandsintilimabplussoxasperioperativetherapyforlocallyresectableadvancedgastricgastroesophagealjunctionadenocarcinomastudyprotocolforaprospectivesinglearmphaseiiclinicaltrial |