Synergistic Effects of PD-1 Antibody and Chemotherapy Followed by Surgery in Limited-metastatic G/GEJ Adenocarcinoma
NCT Number: NCT06468280
Acronym: ROSETTE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Gastric Cancer|GastroEsophageal Cancer
Interventions: PROCEDURE: Radical surgery|DRUG: PD-1 Monoclonal Antibody|DRUG: XELOX Chemotherapy Regimen|PROCEDURE: Local Treatment
Sponsor: Shanghai Zhongshan Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 82
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07
Completion Date: 2028-07
Locations: Zhongshan Hospital Fudan University, Shanghai, Shanghai City, 200032, China

Summary:
The objective of this trial is to compare the efficacy of a comprehensive treatment strategy involving PD-1 monoclonal antibody combined with XELOX chemotherapy followed by radical resection surgery, versus simple systemic treatment in patients with limited distant metastasis of gastric adenocarcinoma/gastroesophageal junction adenocarcinoma.

After enrollment and successful screening, eligible participants will be randomized in a 1:1 ratio into a surgical arm and a non-surgical arm, and will undergo the following treatment:

Surgical Arm:

1. Phase 1 Systemic Therapy: Administration of PD-1 monoclonal antibody in combination with XELOX chemotherapy for cycles 1-4.
2. Surgery: Performing a D2 standard gastrectomy for gastric cancer and radical resection of resectable metastatic lesions.
3. Phase 2 Systemic Therapy: Continuation of PD-1 monoclonal antibody combined with XELOX chemotherapy for cycles 5-8, followed by maintenance therapy with PD-1 monoclonal antibody and capecitabine monotherapy from the 9th cycle until two years post-enrollment.
4. During phase 2 systemic therapy, concurrent local treatments for unresected metastatic lesions are permitted, including radiotherapy, interventional embolization, radiofrequency ablation, and hyperthermic intraperitoneal chemotherapy (HIPEC).

Non-Surgical Arm:

1. Phase 1 Systemic Therapy: Administration of PD-1 monoclonal antibody in combination with XELOX chemotherapy for cycles 1-4.
2. Phase 2 Systemic Therapy: Continuation of PD-1 monoclonal antibody combined with XELOX chemotherapy for cycles 5-8, followed by maintenance therapy with PD-1 monoclonal antibody and capecitabine monotherapy from the 9th cycle until two years post-enrollment.

Primary Outcome Measures: Event-Free Survival (EFS) Rate, Defined as the time from randomization to the first occurrence of any event, including disease progression (local progression, local recurrence, progression of existing distant metastatic lesions, or the emergence of new distant metastases) or death from any cause., 1 year from the time of randomization
Secondary Outcome Measures: Objective Response Rate (ORR), The proportion of subjects achieving complete response (CR) or partial response (PR) after completing phase I systemic treatment., From randomization to the date of completing phase 1 systemic treatment, an average of 12 weeks.|Disease Control Rate (DCR), The proportion of subjects achieving CR, PR, or stable disease (SD) after completing phase I systemic treatment., From randomization to the date of completing phase 1 systemic treatment, an average of 12 weeks.|Pathological Complete Response (pCR) Rate, The proportion of surgical cohort subjects with no residual tumor cells and no positive lymph nodes (ypT0N0) in the primary tumor specimen. Non-surgical subjects in the surgical cohort are considered non-pCR., From randomization to the date of surgery, an average of 14 weeks.|Major Pathologic Response Rate (MPR), The proportion of surgical cohort subjects with residual tumor cells \<10% in the primary tumor specimen based on the Becker tumor regression grading (TRG) standard (1a-1b). Non-surgical subjects in the surgical cohort are considered non-MPR., From randomization to the date of surgery, an average of 14 weeks.|R0 Resection Rate, R0 resection is defined as no tumor at the gross or microscopic resection margins following standard D2 lymphadenectomy gastrectomy., From randomization to the date of surgery, an average of 14 weeks.|Overall Survival (OS), Time from randomization to death from any cause. Survivors are censored at the last known survival date., Up to 4 years follow-up