A Randomized, Controlled, Multicenter Phase II Study of Conversion Therapy Combined With Surgery and Radiotherapy for Retroperitoneal Lymph Node Metastases in Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a randomized, controlled, multicenter phase II clinical trial evaluating the efficacy and safety of conversion therapy combined with radical gastrectomy and adjuvant radiotherapy targeting para-aortic (station 16) lymph nodes in patients with gastric adenocarcinoma and isolated station 16 nodal metastases. Eligible participants must have no evidence of peritoneal dissemination, visceral metastases, or non-regional lymphatic spread. Based on PD-L1 combined positive score (CPS), patients in the experimental arm will receive systemic therapy with SOX (S-1 plus oxaliplatin) with or without a PD-1 inhibitor, followed by D2 gastrectomy and postoperative adjuvant SOX chemotherapy, then intensity-modulated radiotherapy (IMRT) to the para-aortic region. The control arm will receive standard chemotherapy with CAPEOX or SOX, with or without immunotherapy, according to CPS status. The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. This study aims to explore whether the addition of locoregional treatment to systemic therapy improves long-term outcomes in this select patient population.
详细描述
This study targets patients with gastric adenocarcinoma characterized by a low metastatic burden-specifically, isolated metastases to para-aortic (station 16) lymph nodes without evidence of peritoneal carcinomatosis, distant organ metastases, or non-regional lymph node involvement. Patients are stratified by PD-L1 combined positive score (CPS ≥1 vs. <1) and receive first-line systemic conversion therapy with the SOX regimen (S-1 plus oxaliplatin), with or without a PD-1 inhibitor. In the experimental arm, patients demonstrating disease control (CR/PR/SD) undergo D2 radical gastrectomy, followed by five cycles of adjuvant SOX and intensity-modulated radiotherapy (IMRT) targeting the station 16 nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions), with concurrent capecitabine or S-1. Maintenance immunotherapy continues for up to one year in CPS ≥1 patients. The control arm receives standard-of-care systemic treatment with CAPEOX or SOX ± immunotherapy, without surgery or radiotherapy. Tumor tissue, peripheral blood, and fecal samples will be collected at multiple time points for exploratory biomarker analyses, including tumor immune microenvironment profiling, tumor mutational burden (TMB), mismatch repair status (MSI), and circulating immune cell subsets. A total of 54 patients will be enrolled (2:1 randomization), with an accrual period of 18 months and 24 months of follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed gastric adenocarcinoma with isolated para-aortic (station 16) lymph node metastasis; pMMR or MSS subtype; ECOG performance status 0-2; Life expectancy ≥ 3 months; Adequate organ function (hematologic, hepatic, renal); Ability to provide tumor tissue for biomarker analysis; Ability to understand and willingness to sign written informed consent; Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during study and for 12 months after treatment; men with partners of childbearing potential must also agree to contraception.
排除标准
- •Evidence of visceral or peritoneal metastasis; MSI-H or dMMR subtype; HER2-positive disease (IHC 3+ or IHC 2+ with FISH positive); Prior systemic anti-tumor therapy; Prior malignancy within 3 years (except adequately treated basal cell/squamous cell carcinoma of the skin or in situ carcinoma); Prior PD-1/PD-L1/CTLA-4 therapy; Participation in another interventional trial within 4 weeks; Active autoimmune disease requiring systemic therapy within past 2 years; Uncontrolled infection, hepatitis B, C, or HIV; CNS metastases or carcinomatous meningitis; Uncontrolled cardiovascular disease (unstable angina, recent MI, NYHA III-IV heart failure, QTc ≥480 ms); Interstitial lung disease or uncontrolled pulmonary disease; Uncontrolled diabetes mellitus (FBG >10 mmol/L); Pregnancy or breastfeeding; Major surgery within 4 weeks prior to randomization; Any other condition that may interfere with protocol compliance or increase risk as judged by the investigator.
研究组 & 干预措施
Conversion therapy + surgery + para-aortic radiotherapy
Patients with isolated para-aortic (station 16) lymph node metastases from gastric adenocarcinoma will receive first-line systemic conversion therapy based on PD-L1 combined positive score (CPS).
- CPS ≥1: 3 cycles of SOX (S-1 plus oxaliplatin) plus a PD-1 inhibitor (every 3 weeks).
- CPS <1: 3 cycles of SOX alone. After ~8 weeks, patients with non-progressive disease (CR/PR/SD) undergo D2 radical gastrectomy, followed by 5 cycles of adjuvant SOX.
Subsequently, patients receive elective intensity-modulated radiotherapy (IMRT) to the para-aortic (station 16) nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions) with concurrent oral capecitabine or S-1.
For CPS ≥1 patients, maintenance PD-1 inhibitor therapy continues for up to 1 year.
干预措施: SOX regimen (Drug)
Conversion therapy + surgery + para-aortic radiotherapy
Patients with isolated para-aortic (station 16) lymph node metastases from gastric adenocarcinoma will receive first-line systemic conversion therapy based on PD-L1 combined positive score (CPS).
- CPS ≥1: 3 cycles of SOX (S-1 plus oxaliplatin) plus a PD-1 inhibitor (every 3 weeks).
- CPS <1: 3 cycles of SOX alone. After ~8 weeks, patients with non-progressive disease (CR/PR/SD) undergo D2 radical gastrectomy, followed by 5 cycles of adjuvant SOX.
Subsequently, patients receive elective intensity-modulated radiotherapy (IMRT) to the para-aortic (station 16) nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions) with concurrent oral capecitabine or S-1.
For CPS ≥1 patients, maintenance PD-1 inhibitor therapy continues for up to 1 year.
干预措施: PD-1 inhibitor (Drug)
Conversion therapy + surgery + para-aortic radiotherapy
Patients with isolated para-aortic (station 16) lymph node metastases from gastric adenocarcinoma will receive first-line systemic conversion therapy based on PD-L1 combined positive score (CPS).
- CPS ≥1: 3 cycles of SOX (S-1 plus oxaliplatin) plus a PD-1 inhibitor (every 3 weeks).
- CPS <1: 3 cycles of SOX alone. After ~8 weeks, patients with non-progressive disease (CR/PR/SD) undergo D2 radical gastrectomy, followed by 5 cycles of adjuvant SOX.
Subsequently, patients receive elective intensity-modulated radiotherapy (IMRT) to the para-aortic (station 16) nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions) with concurrent oral capecitabine or S-1.
For CPS ≥1 patients, maintenance PD-1 inhibitor therapy continues for up to 1 year.
干预措施: Para-aortic lymph node radiotherapy (IMRT to station 16) (Radiation)
Conversion therapy + surgery + para-aortic radiotherapy
Patients with isolated para-aortic (station 16) lymph node metastases from gastric adenocarcinoma will receive first-line systemic conversion therapy based on PD-L1 combined positive score (CPS).
- CPS ≥1: 3 cycles of SOX (S-1 plus oxaliplatin) plus a PD-1 inhibitor (every 3 weeks).
- CPS <1: 3 cycles of SOX alone. After ~8 weeks, patients with non-progressive disease (CR/PR/SD) undergo D2 radical gastrectomy, followed by 5 cycles of adjuvant SOX.
Subsequently, patients receive elective intensity-modulated radiotherapy (IMRT) to the para-aortic (station 16) nodal basin (45-50 Gy/25 fractions; positive nodes 56-60 Gy/25 fractions) with concurrent oral capecitabine or S-1.
For CPS ≥1 patients, maintenance PD-1 inhibitor therapy continues for up to 1 year.
干预措施: Capecitabine / S-1 (radiosensitizer during IMRT) (Drug)
Systemic therapy alone
Patients in this arm will receive systemic therapy without surgery or radiotherapy.
- CPS ≥1: CAPEOX or SOX chemotherapy combined with a PD-1 inhibitor, followed by PD-1 inhibitor maintenance for up to 1 year.
- CPS <1: CAPEOX or SOX chemotherapy alone. Systemic therapy continues until disease progression, unacceptable toxicity, or completion of 8 planned cycles.
干预措施: SOX regimen (Drug)
Systemic therapy alone
Patients in this arm will receive systemic therapy without surgery or radiotherapy.
- CPS ≥1: CAPEOX or SOX chemotherapy combined with a PD-1 inhibitor, followed by PD-1 inhibitor maintenance for up to 1 year.
- CPS <1: CAPEOX or SOX chemotherapy alone. Systemic therapy continues until disease progression, unacceptable toxicity, or completion of 8 planned cycles.
干预措施: CAPEOX regimen (Drug)
Systemic therapy alone
Patients in this arm will receive systemic therapy without surgery or radiotherapy.
- CPS ≥1: CAPEOX or SOX chemotherapy combined with a PD-1 inhibitor, followed by PD-1 inhibitor maintenance for up to 1 year.
- CPS <1: CAPEOX or SOX chemotherapy alone. Systemic therapy continues until disease progression, unacceptable toxicity, or completion of 8 planned cycles.
干预措施: PD-1 inhibitor (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: 2 years
Time from randomization to disease progression according to RECIST 1.1 or death from any cause, whichever occurs first.
Progression-Free Survival (PFS)
时间窗: 2 years
Time from randomization to disease progression according to RECIST 1.1 or death from any cause, whichever occurs first.
次要结局
- Adverse Events (Safety Profile)(Through study completion (approx. 3 years))
- Overall Survival (OS)(Up to 2 years)
- Disease Control Rate (DCR)(Up to 6 months after randomization)
- Objective Response Rate (ORR)(Up to 6 months after randomization)
- Adverse Events (Safety Profile)(Through study completion (approx. 3 years))
研究者
Jinbo Yue
Professor of Radiation Oncology; Principal Investigator
Shandong Cancer Hospital and Institute