Clinical trial NCT07007182: Conversion Therapy Plus Surgery and Radiotherapy for Retroperitoneal Nodal Metastases in Gastric Cancer
Official title: A Randomized, Controlled, Multicenter Phase II Study of Conversion Therapy Combined With Surgery and Radiotherapy for Retroperitoneal Lymph Node Metastases in Gastric Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gastric Adenocarcinoma
Stomach Neoplasms
Keywords: Conversion therapy
Para-aortic lymph nodes
D2 gastrectomy
Radiotherapy
FLOT regimen
Immunotherapy
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2025-06-05
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 will receive systemic therapy (FLOT ± PD-1 inhibitor) in the experimental arm, followed by D2 gastrectomy and intensity-modulated radiotherapy (IMRT) to the para-aortic region. The control arm will receive standard chemotherapy with or without immunotherapy. 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 metastasis, or non-regional lymph node involvement. The trial aims to evaluate the role of integrated local therapies in this context. Patients are stratified by PD-L1 combined positive score (CPS ≥1 vs. \<1) and receive first-line systemic conversion therapy using the FLOT regimen with or without a PD-1 inhibitor. In the experimental arm, patients demonstrating disease control (CR/PR/SD) undergo D2 radical gastrectomy, followed by IMRT targeting the station 16 nodal basin, with concurrent capecitabine. Postoperative adjuvant chemotherapy and immune maintenance therapy are continued. The control group receives standard-of-care systemic treatment with CAPEOX or SOX ± immunotherapy. Tumor tissue, peripheral blood, and fecal samples will be collected at multiple time points for exploratory biomarker analysis, 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.

Eligibility criteria: Inclusion Criteria:

Signed written informed consent before any study-specific procedure; Male or female, age 18-75 years; Histologically confirmed gastric adenocarcinoma with para-aortic (station 16) lymph node metastasis; pMMR or MSS subtype; ECOG performance status 0-2; No prior anti-tumor therapy; At least one measurable lesion according to RECIST 1.1; Tumor tissue available for biomarker analysis; Expected survival ≥3 months; Adequate organ function; Negative pregnancy test for women of childbearing potential; Use of effective contraception during study and 12 months after treatment.

Exclusion Criteria:

Evidence of visceral or peritoneal metastasis; MSI-H or dMMR subtype; HER2 (++ with FISH positive or +++); Prior malignancies (except cured skin basal/squamous cell carcinoma or in situ carcinoma) within 3 years; Prior PD-1/PD-L1/CTLA-4 or similar immunotherapies; Participation in other interventional trials within 4 weeks; Systemic corticosteroid use within 7 days (except physiologic replacement); Active autoimmune disease requiring systemic treatment in past 2 years; Untreated active hepatitis B, HCV, or HIV infection; Active CNS metastases or carcinomatous meningitis; Uncontrolled hypertension, unstable angina, NYHA III-IV heart failure, QTc ≥480ms; Active interstitial lung disease, uncontrolled infections, GI obstruction; Poorly controlled diabetes (FBG \>10 mmol/L); Pregnancy or breastfeeding; Major surgery within 4 weeks before enrollment; Any condition that may interfere with protocol compliance or increase risk as judged by the investigator.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 1 year
measure: Disease Control Rate (DCR)
timeFrame: Up to 1 year
measure: Adverse Events (Safety Profile)
timeFrame: Through study completion (approx. 3 years)
Other outcomes:
Locations:
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jinbo Yue, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: