The purpose of this study is to investigate the safety and efficacy of conversion therapy using HFRT combined with ICT in locally advanced or metastatic unresectable GEJA.
The aim of this study is to investigate whether hypofractionated radiotherapy (HFRT) combined with a PD-1 inhibitor (Sintilimab) and chemotherapy based on the SOX regimen is a safe and well-tolerated conversion strategy for patients with locally advanced or metastatic unresectable gastroesophageal junction adenocarcinoma (GEJA), and whether it can improve the objective response rate (ORR) compared to immunochemotherapy alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
88
In Phase Ib, HFRT will be administered at one of three dose levels: 3 Gy × 5 fractions, 4 Gy × 5 fractions, or 5 Gy × 5 fractions. The recommended dose determined in Phase Ib will be used in Phase II (delivered as 5 fractions).
SOX chemotherapy regimen: Oxaliplatin 130 mg/m² administered by intravenous infusion on Day 1; S-1 administered orally for 14 consecutive days followed by a 7-day rest period. The dosage of S-1 is based on body surface area (BSA): 40 mg twice daily for BSA ≤1.5 m², 50 mg twice daily for BSA between 1.5-1.6 m², and 60 mg twice daily for BSA ≥1.6 m². Each cycle is repeated every 3 weeks.
Sintilimab 200 mg administered by intravenous infusion on Day 1 of each 3-week cycle.
West China Xiamen Hospital, Sichuan University
Xiamen, Fujian, China
RECRUITINGThe Seventh People's Hospital of Chengdu
Chengdu, Sichuan, China
RECRUITINGWest China Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGSafety and tolerability in Phase Ib
Safety will be assessed based on clinical adverse events, vital signs, and abnormalities in laboratory tests during the study period. Adverse events (AEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. All deaths occurring within 90 days after the first dose of treatment or within 30 days after the last dose will be listed along with the causes of death. Laboratory abnormalities will be categorized according to NCI-CTCAE version 5.0. Maximum Tolerated Dose (MTD): If ≥1 out of 3 patients in a given dose cohort experiences radiotherapy-related dose-limiting toxicity (DLT) within 90 days, that dose level will be considered intolerable. The next lower dose level will be defined as the MTD. The MTD cohort must include at least 6 evaluable patients.
Time frame: within 3 months after the HFRT
ORR rate in Phase II
Objective Response Rate (ORR):ORR is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) as determined by investigators based on RECIST version 1.1. The initial CR or PR must be confirmed by repeat imaging at least 4 weeks after the first documentation of response.
Time frame: approximately 4 weeks after the resection of primary lesion
R0 resection rate
number of R0 surgery divide all participants
Time frame: approximately 2 weeks after the resection of primary lesion
DOR (Duration of Response)
Duration from the first documented complete response (CR) or partial response (PR) to the date of disease progression (PD) or death from any cause.
Time frame: Up to 3 years
PFS (Progression-Free Survival)
Time from the first administration of the study treatment to disease progression (PD) or death from any cause, whichever occurs first.
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West China Shangjin Nanfu Hospital, Sichuan University
Chengdu, Sichuan, China
RECRUITINGTime frame: Up to 3 years
OS (Overall Survival)
Time from the initiation of study treatment to death from any cause.
Time frame: Up to 3 years
Adverse Events (AEs)
The incidence, severity, and relationship of adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time frame: From the first dose through 90 days after the last dose
Quality of Life (QoL) - EORTC QLQ-C30
Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
Time frame: At baseline, during treatment, and at predefined follow-up visits