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

NCT ID: NCT07007182

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2030-10-01

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SOX regimen

Intervention Type: 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.

PD-1 inhibitor

Intervention Type: 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.

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

Intervention Type: 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.

Capecitabine / S-1 (radiosensitizer during IMRT)

Intervention Type: 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.

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.

Group Type: ACTIVE_COMPARATOR

SOX regimen

Intervention Type: 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.

CAPEOX regimen

Intervention Type: 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.

PD-1 inhibitor

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

Oxaliplatin + S-1 (tegafur/gimeracil/oteracil); Oxaliplatin + Capecitabine; Anti-PD-1 antibody; IMRT to station 16; Capecitabine (Xeloda), S-1 (tegafur/gimeracil/oteracil)

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinbo Yue

OTHER

Sponsor Role: lead

Responsible Party

Jinbo Yue

Professor of Radiation Oncology; Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jinbo Yue, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Shandong Cancer Hospital and Institute

Jie Chai, MD, PhD

Role: STUDY_CHAIR

Shandong Cancer Hospital and Institute

Central Contacts

Jinbo Yue, MD, PhD

Role: CONTACT

jbyue@sdfmu.edu.cn

053167626442

Other Identifiers

SDZLEC2025-150-02

Identifier Type: -

Identifier Source: org_study_id