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.
1. This clinical trial will be conducted under Simon's optimal two-stage design. The first stage needs 9 participants, if ≥1 participants acquire remission, then the study will move on to the second stage and enroll the rest 10 participants. Taking into account a drop-out rate of about 5%, we planned to enroll 21 patients. 2. Target population: patients with resectable locally advanced resectable gastric or gastroesophageal junction adenocarcinoma (cT1-2N+M0/T3-T4aNanyM0). 3. Trial design: This is a monocenter, single arm, phase II study to evaluate the efficacy and safety of neoadjuvant chemo-hypofractionated radiotherapy plus PD-1 antibody (Tislelizumab) in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
1. Immunotherapy combined with chemotherapy (2 cycles): Intravenous tislelizumab (200mg, d1, q21d) in combination with XELOX regimen (capecitabine 1000 mg/m2 bid\*14d + oxaliplatin 130mg/m2, d1, q21d); 2. Concurrent radiotherapy: Within one week after the first initiation of chemo-immunotherapy, concurrent hypofractionated radiotherapy will be started: intensity modulated radiotherapy was given for tumors, total dose:30Gy/12f, 2.5Gy/f.
Jiangsu Cancer Hospital
Nanjing, Jiangsu, China
pathological complete remission (pCR) rate
Pathologic complete response was defined as pT0N0M0
Time frame: From date of treatment allocation and during treatment period up to 1 year
Radiographic response
To assess radiographic response to neoadjuvant tislelizumab with concurrent chemoradiotherapy using RECIST 1.1.
Time frame: From date of treatment allocation and during treatment period up to 3 months
The R0 resection rate
Complete Resection With no Tumor Within 1 mm of the Resection Margins (R0) Rate
Time frame: 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.
Time frame: 1 month after the last date of treatment
Postoperative complications
Using the Clavien-Dindo classification
Time frame: 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 frame: 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 frame: 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 frame: Time from the date of study registration to the date of death due to all causes, assessed up to 3 years
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