TAIC FOLFOX for Locally Advanced G/GEJA (TFLAG)

FOLFOX-Based Transarterial Infusion Chemotherapy for Locally Advanced Gastric Cancer and Gastroesophageal Junction Adenocarcinoma: Protocol of an Open-Label, Multicentre, Single-arm, Phase Ⅱ Trial

Gastric cancer is the fifth most common malignancy worldwide in terms of both incidence and mortality. The majority of cases are diagnosed at advanced stage-often presenting with severe complications such as malignant stricture, obstruction, bleeding, and cancer-related malnutrition-which impinge on quality of life and survival outcomes. For patients with unresectable or metastatic gastric cancer and gastroesophageal junction adenocarcinoma (G/GEJA), first-line systemic therapy remains predominantly platinum- and fluoropyrimidine-based combination chemotherapy, and targeted agents or immunotherapy can be added based on the expression of biomarkers. Under this standard approach, the median overall survival (mOS) for localized unresectable G/GEJA is approximately 14-20 months. For metastatic G/GEJA, the prognosis remains poor with an mOS of less than 1 year, despite the proven efficacy of chemotherapeutic agents. Moreover, up to 25% of cancer survivors report a significant decline in quality of life due to gastrointestinal symptoms during, soon after, or many years after treatment.

Interventional oncology approaches-including trans-arterial infusion chemotherapy (TAIC), embolization (TAE), and chemoembolization (TACE)-represent promising locoregional therapeutic strategies. TAIC allows for the direct delivery of cytotoxic agents into the tumor-feeding arteries, thereby maximizing intra-tumoral drug concentration. As one of the most well-recognized applications, hepatic arterial infusion chemotherapy (HAIC) has been demonstrated in liver cancer by elevating local drug exposure, markedly enhancing antitumor efficacy while minimizing systemic adverse effects. Moreover, chemotherapeutic agents may exert secondary systemic activity against clinically or subclinically disseminated metastases upon systemic circulation, contributing to a sustained "secondary chemotherapy" effect. Owing to its favorable safety profile and preserved antitumor activity, TAIC is particularly suited for frail or elderly patients who are ineligible for surgery or conventional systemic chemotherapy.

Given the persistent limitations of current therapeutic paradigms, the feasibility and safety of trans-arterial therapy in the treatment of anti-tumor, hemostasis and obstruction relief for locally advanced G/GEJC remains urgent. The present study aimed to assess the efficacy and safety of TAIC for locally advanced G/GEJA.

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Junction Adenocarcinoma; Gastric Cancer (Diagnosis)
• Intervention / Treatment: Procedure: TAIC; Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Sun, PhD; Phone Number: +86 15010797262; Email: 632739616@qq.com
• Study Contact Backup: Name: Quanda Liu, PhD; Email: quandaliu@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Department of General Surgery, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St, West-city District, Beijing, China
    • Contact: Yan Sun, PhD; Phone Number: +86 15010797262; Email: 6327391616@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Pathologically diagnosed with G/GEJA
• Confirmed by the surgeon as initially unresectable advanced G/GEJC
• Contraindicated to surgery due to frailty or comorbidities
• Expected survival period ≥ 3 months

Exclusion Criteria:

• Primary malignant tumors
• Gastrointestinal obstruction caused by lesions in the distal stomach, duodenum, pancreas or other organs
• Acute infection, severe liver or kidney dysfunction or coagulation disorder
• Allergic to the drugs or with mental disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: the TAIC group; Patients in the TAIC group will undergo FOLFOX-based TAIC at weeks 0 and 4 and receive FOLFOX-based IVC at weeks 2 and 6. The FOLFOX-based TAIC consists of oxaliplatin (85 mg/m²) administered as a 2-hour transarterial infusion, leucovorin (400 mg/m²) administered as a 2-hour transarterial infusion, and fluorouracil (2400 mg/m²) administered as a 44-hour transarterial infusion. According to the results of the genetic mutation status, HER2-positive patients are administered trastuzumab in combination every cycle.

Procedure: TAIC; The Seldinger method was used to insert a vascular sheath through the unilateral femoral artery. A 5 F angiographic catheter (C2, RLG, or RH TYPE, Cook Corporation, Bloomington, IN, USA) was inserted into left gastric, short gastric, and esophageal proper arteries under fluoroscopy guidance, and the condition of each branch vessel was visualized by catheter angiography. Then a 2.7 F microcatheter was introduced into the artery that delivered blood supply to the tumor using the coaxial catheter technology. TAIC were performed based on the blood supply and staining degree of the tumor. For the target vessel, by selective catheterization and DSA (Digital Subtraction Angiography), the vascular distribution and staining degree of the tumor can be directly observed.; Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); Patients in the TAIC group will undergo FOLFOX-based TAIC at weeks 0 and 4 and receive FOLFOX-based IVC at weeks 2 and 6. The FOLFOX-based TAIC consists of oxaliplatin (85 mg/m²) administered as a 2-hour transarterial infusion, leucovorin (400 mg/m²) administered as a 2-hour transarterial infusion, and fluorouracil (2400 mg/m²) administered as a 44-hour transarterial infusion. According to the results of the genetic mutation status, HER2-positive patients are administered trastuzumab in combination every cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The quality of life	The quality of life was assessed using the EORTC QLQ-C30. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status /QoL represents a high QoL, but a high score for a symptom scale /item represents a high level of symptomatology / problems.	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	According to RECIST1.1, DCR (disease control rate) was defined as the sum of complete remission, partial response, and stable disease.	The DCR is assessed at 4 and 8 weeks by the local investigator.
ORR		ORR is defined as the percentage of patients with complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1.The ORR is assessed at 4 and 8 weeks by the local investigator.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The patients' dysphagia degree	The patients' dysphagia degree was evaluated based on the Stooler Dysphagia Grading Scale . The Stooler Dysphagia Grading Scale (often referred to as the Stooler Classification) is a clinical assessment tool primarily used to evaluate the severity of dysphagia (swallowing difficulties), particularly in patients with esophageal cancer or other conditions causing progressive obstruction. It categorizes swallowing ability into five distinct levels based on the type of food the patient can tolerate. Grade 0 Normal Swallowing. Grade 1 Mild Dysphagia. Grade 2 Moderate Dysphagia. Grade 3 Severe Dysphagia. Grade 4 Complete Obstruction.	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.
The general condition of the patients	The Eastern Cooperative Oncology Group (ECOG) performance status. ECOG 0-1: Patients generally have good functional status. ECOG 2: Patients have compromised functional status. ECOG ≥3: Patients are generally considered unfit for aggressive cytotoxic chemotherapy due to poor tolerance and increased risk of severe adverse events.	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.
OS	Overall Survival (OS) was used as the outcome measure.	From enrollment until the date of death from any cause, assessed up to 100 months
Pathological response	Pathological response was assessed using surgical specimens according to the Becker's tumor regression grade system	Surgical resectability assessment should be performed within 2 weeks after the completion of the entire treatment cycle, and pathological response should be conducted if surgery is performed.
The nutritional status	The nutritional status was evaluated using the NRS-2002. NRS-2002 is a standardized tool designed to identify hospital patients who are at nutritional risk. Total Score ≥ 3: Indicates the presence of nutritional risk. Total Score < 3: Indicates no current nutritional risk.	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.
Adverse events	Adverse events were classified according to the Common Terms Criteria for Adverse Events (V 6.0).	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.
Frailty	CFS (clinical frailty scale) utilizes a 9-point scale. Level 1 (Very Fit) to Level 9 (Terminally Ill).	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.
Grip strength	Hand grip strength is a convenient measure for both clinical practice. Grip strength is assessed using a digital hand dynamometer model. The patient should be comfortably seated with the elbow supported at an angle of 90 degrees to the body under the seated method. Grip strength was tested 3 consecutive times consisting of a grip duration of three seconds with a one-minute rest in between. Alternating bilateral assessment of hands should be performed with no warm-up tests. The measured grip value for each hand defined as the average value obtained from repeated measures. The kilogram (kg) is the only unit of measurement.	From enrollment to the end of treatment at 10 weeks, 3 days before each administration period and within 2 weeks after the end of the treatment.

Collaborators and Investigators

• Sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
• Investigators: Study Director: Quanda Liu, PhD, Guanganmen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Unresectable Gastric cancer; Esophagogastric junction adenocarcinoma; Transarterial infusion chemotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pathological Conditions, Signs and Symptoms; Stomach Neoplasms; Disease; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; Folfox protocol
• Other Study ID Numbers: 2025-276-KY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators agree to allow the auditors/inspectors/monitors to have direct access to the trial records for review. The investigator will make every effort to help with the performance of the audits and inspections, giving access to all necessary facilities, data, and documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No