Synergistic Effects of PD-1 Antibody and Chemotherapy/Targeted Therapy Followed by Surgery-centric Local Treatment in Patients With Limited-metastatic Gastric Cancer

Sponsor
Shanghai Zhongshan Hospital
Study ID
NCT06468280
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 79 Years
Healthy Volunteers
Not accepted

Interventions

  • Local treatment (Surgical) — PROCEDURE
    Radical gastrectomy with standard D2 lymphadenectomy will be performed, along with radical surgery for resectable metastatic lesions.
  • PD-1 Monoclonal Antibody — DRUG
    PD-1 monoclonal antibody will be administered at a dosage of 200 mg via intravenous infusion (or according to the prescribing information of specific drug), once every cycle, each cycle spanning three weeks. The specific PD-1 antibody used will be determined by the investigators based on clinical considerations. Potential options include Sintilimab, Tislelizumab, or other approved PD-1 antibody products indicated for the treatment of metastatic gastric or gastroesophageal adenocarcinoma.
  • XELOX/SOX Chemotherapy Regimen — DRUG
    Oxaliplatin: 130 mg/m² administered via a 3-hour intravenous infusion on D1 of each 3-week cycle. Capecitabine: 1000 mg/m² taken orally twice daily. The first dose is administered on the evening of D1, and the last dose on the morning of D15, consisting of 2 weeks of treatment and a 1-week break in each 3-week cycle. S-1: 40 mg/m² taken orally twice daily. The first dose is administered on the evening of D1, and the last dose on the morning of D15, consisting of 2 weeks of treatment and a 1-week break in each 3-week cycle. During the maintainance phase, only capecitabine/S-1 will be administered.
  • Local Treatment (Non-surgical) — PROCEDURE
    Additional local treatment for unresected metastatic lesions during phase 2 systemic therapy is permitted, including: * Bone metastasis, distant lymph nodes, adrenal metastasis: Radiation therapy. * Lung and liver metastasis: Radiofrequency ablation, interventional embolization, or radiation therapy. * Peritoneal metastasis: Hyperthermic intraperitoneal chemotherapy (HIPEC). * Other metastatic lesions: Non-surgical treatment options discussed by the multidisciplinary team.
  • Trastuzumab — DRUG
    For HER2-positive patients, the dosing regimen for the addition of trastuzumab is as follows: During the combination phase with XELOX/SOX chemotherapy: 8 mg/kg administered as an intravenous infusion on D1. During the maintenance phase with capecitabine/S-1: 6 mg/kg administered as an intravenous infusion on D1. This is repeated once every 3 weeks.
  • Zolbetuximab — DRUG
    For patients with Claudin18.2-positive expression (IHC 2-3+ in ≥75% of tumor cells), Zolbetuximab may be added with the following dosing regimen: First cycle: 800 mg/m² administered as an intravenous infusion on D1. Subsequent cycles: 600 mg/m² administered as an intravenous infusion on D1. This is repeated once every 3 weeks.

Study Details

ROSETTE trial is an open-label, randomized phase II study designed to investigate treatment strategies for patients with limited metastatic gastric or gastroesophageal adenocarcinoma. Eligible patients are randomized to receive either systemic treatment followed by surgeon-led local treatment, or systemic treatment alone. Systemic treatment combines immunotherapy with chemotherapy, with or without targeted therapy, while the surgeon-led local treatment utilizes a surgery-centric, multi-modality approach involving resection of both primary and metastatic tumors where feasible. For unresected or unresectable metastatic lesions, alternative local therapies are provided. The primary endpoint is the 1-year event-free survival (EFS) rate. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), extended EFS, overall survival (OS), pathologic complete response rate (pCR), major pathologic response rate (MPR), and R0 resection rate.

Key Dates

Start date
Nov 8, 2024
Status verified
Jan 2026
Primary completion
Dec 31, 2027
Completion
Dec 31, 2028

Study Design

Enrollment
84 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Local Treatment Arm (Arm A)
    In Phase 1, patients will receive four cycles of PD-1 antibody in combination with chemotherapy, with or without targeted therapy. Following this phase, a radiologic assessment will evaluate disease progression status. Patients identified as not experiencing progression will proceed with the study treatments. Subsequently, they will undergo surgeon-led local treatment, which may include standard D2 gastrectomy and metastasectomy when feasible. Non-surgical local treatments may also be administered to address unresected or unresectable metastatic lesions, either concurrently or sequentially with surgery. After surgical intervention, patients will receive up to four additional cycles of treatment, followed by maintenance therapy during Phase 2 of the systemic treatment. The total treatment duration may extend up to two years from the date of enrollment.
  • Active Comparator: Systemic Treatment Arm (Arm B)
    In Phase 1, patients will receive four cycles of PD-1 antibody in conjunction with chemotherapy, with or without targeted therapy. Following this phase, a radiologic assessment will evaluate the disease progression status. Patients classified as not experiencing progression-defined as the absence of local progression, advancement of existing distant metastases, or the emergence of new distant metastatic lesions-will continue with the study treatments. In Phase 2, participants will receive an additional up to four cycles of treatment, followed by maintenance therapy. The total treatment duration could extend up to two years from the date of enrollment.

Primary Outcome Measure

Event-Free Survival (EFS) Rate [ Time Frame: 1 year from the time of randomization ]

Central Contacts

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