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The goal of this clinical trial is to evaluate the efficacy and safety of the multimodal treatment, which includes radiotherapy, chemotherapy and anti-PD-1 immunotherapy. The trial is designed using a pick-the-winner strategy.
The main questions it aims to answer are:
Participants will receive HFRT or PULSAR for the primary lesion and positive lymph nodes, combined with CAPOX and anti-PD-1 immunotherapy. Then, reassessment will be performed within 4 weeks afterwards. For resectable participants, surgical resections will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HFRT | Experimental | Participants will receive upfront hypofractionated radiotherapy (HFRT) of the primary lesion and positive lymph nodes (24 Gy/6 fractions). Afterwards, systemic therapy consisted of CAPOX and PD-1 antibodies will be administered every three weeks, for at least 3 cycles. Then, reassessment will be performed within 4 weeks afterwards. For resectable participants, surgical resections of primary lesion will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT. |
|
| PULSAR | Experimental | Participants will receive treatment every three weeks, for at least 3 cycles. Each cycle of treatment consists of irradiation (6 Gy/1 fraction) to the primary lesion and positive lymph nodes on day 1, and systemic therapy consisted of CAPOX and PD-1 antibodies will be administered on day 2. Then, reassessment was performed within 4 weeks afterwards. For resectable participants, surgical resections of primary lesion will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HFRT targeted to the primary lesion and positive lymph nodes | Radiation | Hypofractionated radiotherapy (HFRT) targeted to the primary lesion and positive lymph nodes (4Gy × 6 fractions) |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological complete regression (pCR) rate | Proportion of patients who attain pCR after preoperative treatment. | 6 months after the enrollment of the last subject |
| Measure | Description | Time Frame |
|---|---|---|
| R0 resection rate | Proportion of patients who achieve R0 resection. | 6 months after the enrollment of the last subject |
| Objective response rate (ORR) | Proportion of patients with complete response (CR) or partial response (PR) to preoperative therapy. ORR will be evaluated using RESIST1.1 |
| Measure | Description | Time Frame |
|---|---|---|
| To measure changes in tumor immune microenvironment (TIME) by single-cell sequencing before and after protocol therapy and correlate with the efficacy of the protocol therapy | 36 months after the recruitment of the last subject | |
| The association of baseline PD-L1 CPS, TMB, MSI/MMR status, and EBER status with the efficacy of the protocol therapy |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Shanghai | 200032 | China |
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| PULSAR targeted to the primary lesion and positive lymph nodes | Radiation | Irradiation targeted to the primary lesion and positive lymph nodes (6 Gy/1 fraction) |
|
| Anti-PD-1 monoclonal antibody | Drug | The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status. The commonly used anti-PD-1 mAb usages are as follows: Nivolumab, 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Sintilimab, 200mg solution intravenously once daily, Q3W. |
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| Chemotherapy | Drug | CAPOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks |
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| R0 total/subtotal gastrectomy with D2 lymphadenectomy | Procedure | For resectable participants, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion. |
|
| 6 months after the recruitment of the last subject |
| Event-free survival (EFS) | EFS is defined as the time interval from enrollment to an event which includes disease progression, discontinuation of the treatment for any reason, or death. | 36 months after the enrollment of the last subject |
| Overall survival (OS) | OS is defined as the time interval from enrollment to death of any reason or censoring. | 36 months after the enrollment of the last subject |
| Toxicities | Number of participants with treatment-related adverse events (TrAEs) reported between the first dose and 28 days after the last dose of study therapy as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. | From the time of enrollment, assessed up to 28 days after the last dose of study therapy |
| Surgical morbidity | Surgery related adverse events (SRAEs) refer to complications which happen during or one month after surgery. Severe complications after surgery will be documented and classified by Clavien-Dindo classification, such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, and incision complications (infection, bleeding, rupture). | During or one month after surgery |
| Surgical mortality | Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death. | During or one month after surgery |
| 36 months after the enrollment of the last subject |
| To study the association between gut microbiota and the efficacy of the protocol therapy | 36 months after the enrollment of the last subject |
| ID | Term |
|---|---|
| C000711728 | spartalizumab |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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