Conversion Therapy Plus Surgery and Radiotherapy for Retroperitoneal Nodal Metastases in Gastric Cancer

Jinbo Yue

Status and phase: Not yet enrolling; Phase 2

Conditions: Stomach Neoplasms; Gastric Adenocarcinoma

Treatments: Drug: Capecitabine / S-1 (radiosensitizer during IMRT); Drug: CAPEOX regimen; Drug: SOX regimen; Radiation: Para-aortic lymph node radiotherapy (IMRT to station 16); Drug: PD-1 inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT07007182

SDZLEC2025-150-02

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 54 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

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.

Exclusion Criteria:

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Conversion therapy + surgery + para-aortic radiotherapy

Experimental group

Description:

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.

Treatment:

Drug: PD-1 inhibitor

Radiation: Para-aortic lymph node radiotherapy (IMRT to station 16)

Drug: SOX regimen

Drug: Capecitabine / S-1 (radiosensitizer during IMRT)

Systemic therapy alone

Active Comparator group

Description:

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.

Treatment:

Drug: PD-1 inhibitor

Drug: SOX regimen

Drug: CAPEOX regimen