NCT07257380

Feasibility of Circulating Tumor DNA Based Minimal Residual Disease-Guided Adjuvant Therapy in Locally Advanced Gastric Cancer With Neoadjuvant Treatment: An Adaptive Trial (MRD-ATLAS)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Shanghai Zhongshan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 79 Years
• Healthy volunteers: Not accepted

Summary

Standard treatment for locally advanced gastric cancer currently involves surgery combined with chemotherapy administered both before and after the operation. However, post-surgery (adjuvant) chemotherapy often causes severe side effects, and it is unclear if all patients truly benefit from it. Recent research, such as the SPACE-FLOT study, suggests that patients who respond well to pre-surgery treatment might not actually benefit from further aggressive treatment after surgery; in these cases, additional therapy may only increase the risk of side effects without improving survival. To address this, researchers are investigating circulating tumor DNA (ctDNA) testing, which detects microscopic traces of cancer (Molecular Residual Disease, or MRD) in the blood. The utility of ctDNA is supported by extensive research: In Colorectal Cancer: The GALAXY study demonstrated that ctDNA status accurately predicts patient survival and identifies who benefits from chemotherapy. Furthermore, the DYNAMIC study showed that using ctDNA to guide treatment decisions significantly reduced the use of unnecessary chemotherapy without compromising patient survival. In Gastric Cancer: Studies such as MENCA-GC, CRITICS, and PLAGAST have confirmed that post-surgery ctDNA is a strong predictor of patient prognosis. Additionally, the MRD-GATE study provided preliminary evidence that ctDNA-guided strategies can reduce unnecessary chemotherapy in the adjuvant setting. Building on this evidence, this study applies ctDNA testing to the standard perioperative treatment model for gastric cancer. The primary objective is to determine if a ctDNA-guided strategy can identify patients who can safely forgo post-surgery chemotherapy, thereby reducing treatment toxicity and unnecessary usage, without sacrificing long-term survival outcomes.

Conditions

• Gastric / Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Standard neoadjuvant therapy	Participants will receive 4 cycles of neoadjuvant therapy based on CSCO/NCCN guidelines. The specific regimen is determined by molecular characteristics and clinical practice: 1. Chemotherapy: Options include SOX, DOS, FLOT, XELOX (CapeOx), or FOLFOX. 2. HER2-Positive: Trastuzumab combined with chemotherapy, with or without immunotherapy. 3. Immunotherapy: PD-(L)1 inhibitors may be administered as monotherapy or in combination with chemotherapy. Dosages and administration follow standard pharmaceutical labeling and institutional protocols.
PROCEDURE	Radical gastrectomy	Radical gastrectomy with standard D2 lymphadenectomy will be performed.
DRUG	Standard adjuvant therapy	Postoperative adjuvant therapy for the control group is determined by an experienced clinician based on standard clinical guidelines (e.g., CSCO, NCCN) and the patient's clinical status. The decision to administer adjuvant therapy, along with the specific regimen, is made at the discretion of experienced clinicians. If indicated, therapy typically begins 4-6 weeks post-surgery and consists of 4 cycles. The regimen generally mirrors the neoadjuvant therapy received and may include: 1. Chemotherapy: Options include SOX, DOS, FLOT, XELOX (CapeOx), or FOLFOX. 2. HER2-Positive: Trastuzumab combined with chemotherapy, with or without immunotherapy. 3. Immunotherapy: PD-(L)1 inhibitors may be administered as monotherapy or in combination with chemotherapy. Dosages and administration follow standard pharmaceutical labeling and institutional protocols. Patients deemed unsuitable for adjuvant therapy by experienced clinicians will undergo observation.
DRUG	ctDNA-MRD-guided adjuvant therapy	Participants in the Experimental Arm will initially receive 4 cycles of neoadjuvant therapy followed by D2 radical gastrectomy. Postoperative management is strictly guided by ctDNA MRD status assessed at 4 weeks post-surgery: 1. ctDNA MRD-Negative Subgroup: Participants will not receive adjuvant therapy and will undergo active surveillance (observation). 2. ctDNA MRD-Positive Subgroup: Participants will receive 4 cycles of adjuvant therapy, initiating 4-6 weeks after surgery. The regimen generally mirrors the neoadjuvant therapy and is selected based on clinical guidelines (e.g., CSCO/NCCN). Options include: Chemotherapy: SOX, XELOX (CapeOx), FLOT, DOS, or FOLFOX . Targeted/Immunotherapy: Agents such as Trastuzumab (for HER2+) or PD-(L)1 inhibitors may be included if clinically indicated.

Timeline

• Start date: 2025-12-30
• Primary completion: 2029-12-30
• Completion: 2029-12-30
• First posted: 2025-12-02
• Last updated: 2025-12-02

Locations

1 site across 1 country: China