PMID- 38022553 OWN - NLM STAT- MEDLINE DCOM- 20231201 LR - 20240320 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as an adjuvant therapy for ctDNA-positive gastric and gastroesophageal junction adenocarcinoma: a protocol for a randomized, controlled, multicenter phase II clinical trial (EXPLORING study). PG - 1232858 LID - 10.3389/fimmu.2023.1232858 [doi] LID - 1232858 AB - BACKGROUND: The efficacy of current adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. ctDNA could serve as a potential marker to identify patients who are at higher risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly improve clinical outcome, albeit such evidence is rare in GA/GEJA. Here, we intend to explore the clinical benefit of the reinforcement of adjuvant immunotherapy and antiangiogenics alongside with chemotherapy in patients who are deemed in high risk of recurrence by ctDNA analysis, which might shed light on further improvements in adjuvant therapy for GA/GEJA. METHODS/DESIGN: This study is designed as a prospective, multicenter, randomized, controlled phase II study in patients histologically or cytologically diagnosed with GA/GEJA who underwent D2 gastrectomy and achieved R0 or R1 resection. From February 2022, a total of 300 stage III patients will be enrolled and subjected according to ctDNA sequencing results, and those with positive results will subsequently be randomized 1:1 to arm A or B. Patients in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while patients in arm B will receive XELOX alone for 6-8 cycles. ctDNA-negative patients will be assigned to arm C, and patients who are ctDNA positive but failed in randomization will be assigned to arm D. Patients in arms C and D will receive the investigator's choice of therapy. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the DFS of ctDNA positive patients versus ctDNA negative patients, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules on the treatment response, adverse events (AEs), and the impact of nutrition status or exercise on recurrence. DISCUSSION: We expect that ctDNA would be a strong prognostic factor and ctDNA-positive patients are at higher risk of relapse than ctDNA-negative patients. The addition of anlotinib and penpulimab to XELOX, may contribute to delaying relapse in ctDNA-positive patients. TRIAL REGISTRATION: https://www.clinicaltrials.gov, identifier NCT05494060. CI - Copyright (c) 2023 Chen, Zhang, Han, Tang, Guo, Li, Xie, Xu, Zhang, Tian, Pan, Shu, Ma and Chen. FAU - Chen, Yizhang AU - Chen Y AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. AD - The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China. FAU - Zhang, Jiaguang AU - Zhang J AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Han, Gaohua AU - Han G AD - Department of Oncology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China. FAU - Tang, Jie AU - Tang J AD - Department of Oncology, Liyang People's Hospital, Changzhou, China. FAU - Guo, Fen AU - Guo F AD - Department of Oncology, Suzhou Municipal Hospital, Suzhou, China. FAU - Li, Wei AU - Li W AD - Department of Oncology, The First Affiliated Hospital of Soochow, Suzhow, China. FAU - Xie, Li AU - Xie L AD - Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xu, Hao AU - Xu H AD - Department of Gastric Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zhang, Xinyi AU - Zhang X AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Tian, Yitong AU - Tian Y AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Pan, Lanlan AU - Pan L AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Shu, Yongqian AU - Shu Y AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ma, Ling AU - Ma L AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Chen, Xiaofeng AU - Chen X AD - Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Oncology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China. LA - eng SI - ClinicalTrials.gov/NCT05494060 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231031 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (penpulimab) RN - U3P01618RT (Fluorouracil) RN - 0 (anlotinib) RN - 04ZR38536J (Oxaliplatin) RN - XELOX RN - Adenocarcinoma Of Esophagus SB - IM MH - Humans MH - *Fluorouracil/therapeutic use MH - Prospective Studies MH - Oxaliplatin/therapeutic use MH - Neoplasm Recurrence, Local/drug therapy MH - Esophagogastric Junction MH - *Adenocarcinoma/drug therapy/genetics MH - Recurrence MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - Clinical Trials, Phase II as Topic PMC - PMC10644233 OTO - NOTNLM OT - CtDNA OT - GA/GEJA OT - XELOX adjuvant chemotherapy OT - anlotinib OT - clinical trial OT - penpulimab OT - protocol OT - vascular normalization COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/11/29 18:41 MHDA- 2023/12/01 06:44 PMCR- 2023/01/01 CRDT- 2023/11/29 15:26 PHST- 2023/06/01 00:00 [received] PHST- 2023/10/11 00:00 [accepted] PHST- 2023/12/01 06:44 [medline] PHST- 2023/11/29 18:41 [pubmed] PHST- 2023/11/29 15:26 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1232858 [doi] PST - epublish SO - Front Immunol. 2023 Oct 31;14:1232858. doi: 10.3389/fimmu.2023.1232858. eCollection 2023.