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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Radical gastrectomy with standard D2 lymphadenectomy will be performed, along with radical surgery for resectable metastatic lesions.
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.
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.
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.
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.
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.
Zhongshan Hospital Fudan University
Shanghai, Shanghai City, China
NOT_YET_RECRUITINGZhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGEvent-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.
Time frame: 1 year from the time of randomization
Objective Response Rate (ORR)
The proportion of subjects achieving complete response (CR) or partial response (PR) after completing phase I systemic treatment.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 5 years follow-up
Event-Free Survival (EFS)
Time from randomization to the first occurrence of disease progression (local recurrence, new distant metastasis, or progression of existing metastases) or death from any cause.
Time frame: Up to 5 years follow-up
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