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

NCT07007182 | Recruiting Phase 2

• 1 other identifier: SDZLEC2025-150-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Adenocarcinoma; Stomach Neoplasms

Keywords

Conversion therapy; Para-aortic lymph nodes; D2 gastrectomy; Radiotherapy; SOX regimen; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Time from randomization to disease progression according to RECIST 1.1 or death from any cause, whichever occurs first.

  2 years

Secondary Outcomes (4)

• Overall Survival (OS)

  Up to 2 years

• Objective Response Rate (ORR)

  Up to 6 months after randomization

• Disease Control Rate (DCR)

  Up to 6 months after randomization

• Adverse Events (Safety Profile)

  Through study completion (approx. 3 years)

Study Arms (2)

Conversion therapy + surgery + para-aortic radiotherapy

EXPERIMENTAL

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.

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

Systemic therapy alone

ACTIVE COMPARATOR

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.

Drug: SOX regimen; Drug: CAPEOX regimen; Drug: PD-1 inhibitor

Interventions

SOX regimen DRUG

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.

Also known as: Oxaliplatin + S-1 (tegafur/gimeracil/oteracil)

Conversion therapy + surgery + para-aortic radiotherapy; Systemic therapy alone

CAPEOX regimen DRUG

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.

Also known as: Oxaliplatin + Capecitabine

Systemic therapy alone

PD-1 inhibitor DRUG

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.

Also known as: Anti-PD-1 antibody

Conversion therapy + surgery + para-aortic radiotherapy; Systemic therapy alone

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

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.

Also known as: IMRT to station 16

Conversion therapy + surgery + para-aortic radiotherapy

Capecitabine / S-1 (radiosensitizer during IMRT) DRUG

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.

Also known as: Capecitabine (Xeloda), S-1 (tegafur/gimeracil/oteracil)

Conversion therapy + surgery + para-aortic radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jinbo Yue: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, 250117, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Oxaliplatin; S 1 (combination); Tegafur; XELOX; Capecitabine; Immune Checkpoint Inhibitors; spartalizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Jinbo Yue, MD, PhD

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

• Jie Chai, MD, PhD

  Shandong Cancer Hospital and Institute

  STUDY CHAIR

Central Study Contacts

Jinbo Yue, MD, PhD

CONTACT

053167626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Radiation Oncology; Principal Investigator

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 5, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: May 1, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)