Gastric Cancer, RCT
Conditions
Keywords
gastric cancer, Ivonescimab, neoadjuvant treatment
Brief summary
The purpose of this clinical trial is to evaluate whether perioperative ivonescimab in combination with S-1 and oxaliplatin (SOX) is effective in treating locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study will also assess the safety profile of this treatment regimen. Primary Objective: To determine whether perioperative ivonescimab plus SOX improves the pathological complete response (pCR) rate compared with SOX alone in patients with locally advanced gastric or GEJ adenocarcinoma. Study Design: Participants will be randomly assigned to receive either ivonescimab plus SOX or SOX alone to evaluate the potential added benefit of ivonescimab in this setting. Participation Details: Participants will receive the assigned treatment (ivonescimab plus SOX or SOX alone) every 21 days for approximately 4 months. They will visit the clinic once every 3 weeks for evaluations, laboratory tests, and monitoring. Participants will be asked to keep a daily diary to record any symptoms or side effects experienced during the study.
Detailed description
To evaluate the efficacy and safety of ivonescimab in combination with S-1 and oxaliplatin (SOX) for the treatment of locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant (perioperative) setting, with the goal of improving the pathological complete response (pCR) rate.
Interventions
ivonescimab (20 mg/kg), four 3-week cycles were administered; ivonescimab was not administered in cycle 4. .
DRUGOxaliplatin
Oxaliplatin (130 mg/m², administered intravenously on day 1), four 3-week cycles were administered.
DRUGS-1
S-1 (administered orally twice daily on days 1-14 of each 21-day cycle, with the daily dose determined by body surface area: \<1.25 m², 80 mg/day; ≥1.25 to \<1.5 m², 100 mg/day; ≥1.5 m², 120 mg/day), four 3-week cycles were administered.
Sponsors
Sichuan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Ivonescimab Plus S-1 and Oxaliplatin (SOX)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years. 2. Histologically confirmed gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Clinically staged as T3-4a N+ M0 by computed tomography (CT) or magnetic resonance imaging (MRI). 5. Considered eligible for curative resection. 6. No prior antitumor therapy for the current disease. 7. Adequate organ function, including hepatic, renal, and bone marrow function, as per prespecified laboratory criteria. 8. Expected survival of ≥6 months.
Exclusion criteria
1. Known mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumor. 2. Uncontrolled hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite optimized antihypertensive therapy, or hypertension complicated by acute events (e.g., hypertensive crisis, hypertensive encephalopathy) that cannot be stably controlled. 3. Tumor lesions with a bleeding tendency, including but not limited to: active ulcerative tumor lesions, hematemesis within 2 months prior to informed consent, high risk of major gastrointestinal bleeding as determined by the investigator. 4. History of thromboembolic or arterial/venous vascular events within 6 months prior to enrollment, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism. 5. Gastrointestinal perforation or gastrointestinal obstruction within 6 months prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Total pathological complete response (pCR; ypT0) assessed by investigators, defined as the complete absence of tumor cells in the primary tumor on pathological examination. | Perioperative |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | Through study completion,an average of 2 years | Event-free survival (EFS), defined as the time from randomization to the first occurrence of relapse, metastasis, or death from any cause; |
| major pathologic response | Perioperative | defined as ≤10% residual viable tumor cells in the resected primary tumor specimen after neoadjuvant therapy; |
| R0 resection | Perioperative | defined as microscopically margin-negative resection |
| overall survival (OS) | Through study completion,an average of 2 years | defined as the time from randomization to death from any cause; |
| disease-free survival (DFS) | Through study completion,an average of 2 years | defined as the time from the post-surgery baseline scan to the first occurrence of relapse, metastasis, or death from any cause |
| safety | Through study completion,an average of 2 years | Treatment-related adverse events (TRAEs) with potential immunologic etiology were categorized and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0) |
| surgery-related complications | Through study completion,an average of 2 years | were graded according to the Clavien-Dindo classification; |
| An exploratory endpoint | Through study completion,an average of 2 years | was the evaluation of potential predictive biomarkers associated with treatment response |
| Quality of life | Perioperative | Quality of life was assessed using the EORTC QLQ-STO22 and EORTC QLQ-C30 questionnaires, administered at three time points: within one week before initiation of neoadjuvant therapy, within one week before the fourth neoadjuvant therapy cycle, and at 30 days postoperatively (±3 days) |
Countries
China
Contacts
CONTACTHu Qiancheng, MD
CONTACTGou Hongfeng
PRINCIPAL_INVESTIGATORGou Hongfeng
Gastric Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan, China.
Outcome results
None listed