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Gastric cancer is the third leading cause of death due to cancer worldwide. Although the consensus on the surgical treatment has resulted in the improvement of curative effect during the past decades, controversies remained for the perioperative therapy of gastric cancer, especially in the selection of the optimal neoadjuvant regimens. Immunotherapy with anti-programmed cell death-1 (PD-1) antibody has demonstrated moderate efficacy in selected patients with advanced gastric adenocarcinoma. Hypofractionated radiotherapy (HypoRT) may act synergistically with immunotherapy to enhance antitumor responses. This phase II trial study want to exploit the efficacy and safety to give PD-1 antibody (Tislelizumab) with combination chemotherapy and HypoRT before surgery in treating adult patients with gastric or gastroesophageal junction adenocarcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab) | Combination Product |
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| Measure | Description | Time Frame |
|---|---|---|
| pathological complete remission (pCR) rate | Pathologic complete response was defined as pT0N0M0 | From date of treatment allocation and during treatment period up to 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Radiographic response | To assess radiographic response to neoadjuvant tislelizumab with concurrent chemoradiotherapy using RECIST 1.1. | From date of treatment allocation and during treatment period up to 3 months |
| The R0 resection rate |
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Inclusion Criteria:
Exclusion Criteria:
Patients with distant metastasis or unresectable primary lesion.
Received prior treatment or receiving current treatment for this malignancy.
Patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
Perforation / fistula of GI tract in 6 months before recruitment.
Patients with upper GI tract obstruction or functional abnormality or malabsorption syndrome, which can affect absorption of apecitabine.
Patients with active autoimmune disease or history of refractory autoimmune disease.
Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
Pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
Uncontrollable systemic diseases, including diabetes, hypertension, etc.
Severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
Patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
Patients with any cardiovascular risk factors below:
Moderate or severe renal injury [creatinine clearance rate≤50 ml/min (according to Cockroft & Gault equation)], or Scr>ULN.
Dipyrimidine dehydrogenase (DPD) deficiency.
Allergic to any drug in this study.
History of allogeneic stem cell transplantation or organ transplantation.
Use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive therapy in 14 days before recruitment, except patients treated with regimens below: a. steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local application with little systemic absorption; c. short -term (≤ 7 days) steroids for preventing allergy or vomiting.
Vaccinated with live vaccine in 4 weeks before recruitment.
Receiving immune (interleukin, interferon, thymin) treatment or treatment of other trials in 28 days before recruitment.
Receiving palliative radiation in 14 days before recruitment.
History of anti PD-1, PD-L1, PD-L2 or any other specific T cell co-stimulation or checkpoint pathway targeted treatment.
Patients who lose ≥20% of body weight within 2 months before enrollment.
For patients with uncontrolled epilepsy, CNS diseases or history of mental disorder, researchers should evaluate whether their diseases will impede their signing of informed consent or compliance of treatment.
Existing of potential situation which will impede drug administration or affect toxicity analysis or alcohol/ drug abuse.
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| Name | Affiliation | Role |
|---|---|---|
| Cheng Chen, doctor | Jiangsu Cancer Institute & Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jiangsu Cancer Hospital | Nanjing | Jiangsu | 210009 | China |
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| ID | Term |
|---|---|
| C000707970 | tislelizumab |
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Complete Resection With no Tumor Within 1 mm of the Resection Margins (R0) Rate
| Up to 3 years |
| Safety of neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab) Safety of neoadjuvant therapy | Adverse events (AE) of neoadjuvant therapy will be graded and documented according to NCI-CTCAE v5.0 from the beginning of treatment to 1 month after the last date of treatment. | 1 month after the last date of treatment |
| Postoperative complications | Using the Clavien-Dindo classification | AEs of surgery refer to complications which happen during or in 30 days after operation. |
| Time to Relapse (TTR) | The median TTR and confidence interval will be estimated using the method of Kaplan-Meier | Time from the date of study registration to the date of 1st documented relapse/recurrence among patients who achieve R- resection, assessed up to 3 years |
| Progression-free Survival (PFS) | The distribution of PFS will be estimated using the method of Kaplan-Meier. | Time from the date of study registration to the date of death due to all causes, recurrences if R0 resections are achieved, progression disease before undergoing surgery, or R1/R2 resection at surgery, whichever comes first, assessed up to 3 years |
| Overall Survival (OS) | The distribution of OS will be estimated using the method of Kaplan-Meier. | Time from the date of study registration to the date of death due to all causes, assessed up to 3 years |