NCT06980389

Node-Sparing Short-Course Radiotherapy Plus First-Line Therapy and PD-1 Inhibitor in Unresectable/Metastastic pMMR/MSS Gastric Cancer (MODIFI-GC)

Node-Sparing Short-Course Radiotherapy Followed by First-Line Therapy Plus PD-1 Inhibitor in Unresectable Locally Advanced or Metastatic pMMR/MSS Gastric Cancer: A Prospective, Randomized, Controlled Phase II Trial (MODIFI-GC)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 176 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

For patients with unresectable locally advanced or metastatic gastric cancer, systemic anti-tumor therapy remains the mainstay of treatment. Combining chemotherapy with immune checkpoint inhibitors has gradually become the standard first-line treatment for advanced gastric cancer. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of MSS/pMMR tumors to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for the anti-tumor activity of PD-1 blockade; however, radiation-induced damage and fibrosis may impair lymphatic drainage and local immune responses. Previous studies have suggested that irradiation of the primary tumor combined with immune checkpoint blockade can produce an abscopal effect, mediating regression of distant metastases. This study aims to evaluate whether node-sparing modified short-course radiotherapy followed by chemotherapy and PD-1 blockade can improve 2-year progression-free survival (PFS) in patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.

Conditions

• Immune Checkpoint Therapy
• Radiotherapy
• Metastatic Gastric Carcinoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Node-Sparing Radiotherapy plus first-line therapy	Patients will receive node-sparing modified short-course radiotherapy, followed by standard first-line chemotherapy combined with a PD-1 inhibitor starting 2-5 days after radiotherapy. Treatment will continue until disease progression or the occurrence of unacceptable toxicity.
COMBINATION_PRODUCT	First-line treatment	Patients will receive standard first-line chemotherapy combined with a PD-1 inhibitor. Treatment will continue until disease progression or the occurrence of unacceptable toxicity.

Timeline

• Start date: 2025-05-31
• Primary completion: 2027-12-31
• Completion: 2028-12-31
• First posted: 2025-05-20
• Last updated: 2025-05-20

Locations

1 site across 1 country: China