NCT07007182

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

A Randomized, Controlled, Multicenter Phase II Study of Conversion Therapy Combined With Surgery and Radiotherapy for Retroperitoneal Lymph Node Metastases in Gastric Cancer

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: Jinbo Yue · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Gastric Adenocarcinoma
• Stomach Neoplasms

Interventions

Type	Name	Description
DRUG	SOX regimen	The SOX regimen consists of oxaliplatin 130 mg/m² IV on day 1 plus oral S-1 (tegafur/gimeracil/oteracil) 40-60 mg twice daily, taken on days 1-14 followed by 7 days off, in a 21-day cycle. Experimental arm: 3 cycles before surgery, 5 cycles after surgery. Control arm: up to 8 cycles as standard systemic therapy.
DRUG	CAPEOX regimen	The CAPEOX regimen consists of oxaliplatin 130 mg/m² IV on day 1 plus oral capecitabine 1000 mg/m² twice daily on days 1-14, repeated every 3 weeks (q3w), up to 8 cycles. Used as a standard chemotherapy option in the control arm, with or without PD-1 inhibitor according to PD-L1 CPS score.
DRUG	PD-1 inhibitor	A PD-1 inhibitor is administered intravenously at a fixed dose of 200 mg every 3 weeks. It is combined with SOX in the experimental arm (CPS ≥1 patients) during conversion and adjuvant phases, and with CAPEOX or SOX in the control arm (CPS ≥1 patients). Maintenance PD-1 inhibitor continues for up to 1 year or until disease progression or unacceptable toxicity.
RADIATION	Para-aortic lymph node radiotherapy (IMRT to station 16)	Intensity-modulated radiotherapy (IMRT) is delivered postoperatively to the para-aortic (station 16) nodal basin. Elective nodal basin: 45-50 Gy in 25 fractions Positive nodes: 56-60 Gy in 25 fractions Radiotherapy is given concurrently with oral capecitabine or S-1 as radiosensitizers.
DRUG	Capecitabine / S-1 (radiosensitizer during IMRT)	During para-aortic IMRT, patients receive concurrent oral capecitabine 825 mg/m² twice daily on radiation days, or oral S-1 dosed according to body surface area. These agents are used as radiosensitizers during postoperative radiotherapy.

Timeline

• Start date: 2025-10-01
• Primary completion: 2029-04-01
• Completion: 2030-10-01
• First posted: 2025-06-05
• Last updated: 2025-09-05