Gastric Adenocarcinoma, Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma, Peritoneal Metastasis
Conditions
Keywords
gastric cancer, Peritoneal Metastasis, Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma
Brief summary
For peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma (cT3-4NanyM1), PD-1 antibody combined with chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) can downstage tumor stage, increase the conversion resection rate, and may improve the long-term survival. Tislelizumab, an anti-PD-1 antibody, has recently been proved in the first- and second-line standard treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.In the subgroup analysis of RATIONALE-305 trial, tislelizumab also showed good efficacy in gastric/gastroesophageal junction adenocarcinoma patients with peritoneal metastasis. Combination of tirellizumab,SOX and HIPEC for peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a monocenter, single-arm phase 2 clinical trial to evaluate tolerability, safety and efficacy of perioperative tirellizumab in combination with SOX and HIPEC in peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma.
Detailed description
The incidence of gastric and gastroesophageal junction adenocarcinoma is increasing, and it is one of the most common malignant tumors in China. Surgery is the only possible way to cure gastric and gastroesophageal junction adenocarcinoma. Peritoneal metastasis is one of the most common modes of spread of gastric cancer. For gastric cancer with peritoneal metastasis, surgical treatment alone can not improve overall survival. Perioperative immunotherapy plus chemotherapy can downstage tumor T and N stage, increase the R0 resection rate, and may improve the long-term survival. Currently, surgical treatment combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic chemotherapy has demonstrated promising outcomes in both the treatment and prevention of peritoneal metastasis in gastric cancer. However, the therapeutic effects of immunotherapy combined with chemotherapy and HIPEC for gastric cancer with peritoneal metastasis remains unclear to date. Combination of perioperative tislelizumab and SOX plus HIPEC for peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase conversion resection rate and overall survival. This monocenter, single-arm phase 2 clinical trial aims to evaluate the effectiveness of tislelizumab plus SOX and HIPEC regimens in patients with peritoneal metastatic gastric/gastroesophageal junction adenocarcinoma to determine the optimal therapeutic approach.
Interventions
DRUGTislelizumab
recombinant humanized anti-PD-1 monoclonal antibody for injection; 200mg ivdrip，d1, q3w
DRUGS-1
40\~60mg Bid，d1\~14, q3w
DRUGOxaliplatin
130mg/m2，iv drip for 2h，d1, q3w
DRUGDocetaxel
Docetaxel at a dose of 20 mg/m2 or paclitaxel at a dose of 40 mg/m2 dissolved in 3-5 L of normal saline heated to 43 ± 0.5 °C for HIPEC.(d01-d03,qd,before first cycle of Tislelizumab and SOX)
DRUGPaclitaxel
Paclitaxel at a dose of 40 mg/m2 or docetaxel at a dose of 20 mg/m2 dissolved in 3-5 L of normal saline heated to 43 ± 0.5 °C for HIPEC.(d01-d03,qd,before first cycle of Tislelizumab and SOX)
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Signed informed consent Patients age 18-75 years Histologically CT/MRI confirmed cT3-4NanyM1 gastric or GEJ adenocarcinoma; Peritoneal metastasis was confirmed by laparoscopy (with or without Krukenberg tumor ) The degree of peritoneal metastasis ≤P1b or PCI≤13 points ECOG 0-1, no surgery contraindications; Expected survival ≥3 months;
Exclusion criteria
Prior chemotherapy, radiotherapy, surgery for gastric cancer; Signs of other distant metastases (e.g., liver, lung, bone, supraclavicular lymph, etc.) Significant cardiovascular disease Major surgical procedure within 4 weeks prior to initiation of study treatment Current treatment with anti-viral therapy or HBV Pregnancy or breastfeeding History of malignancy within 5 years prior to screening Present or history of any autoimmune disease or immune deficiency Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent There are active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases, or active bleeding in unresectable tumors Poorly controlled hypertension or diabetes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| One year overall survival | From the initiation date of first cycle to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R0 resection rate | Time Frame: From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks. | Proportion of enrolled subjects who undergo microscopically margin-negative (R0) resection. |
| Major Pathological Response Rate (MPR) | From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks. | The proportion of patients with less than 10% residual viable tumor cells in the resected specimen. |
| Objective Response Rate (ORR) | From the initiation date of first cycle (each cycle is 21 days) to the date of last cycle, an average of 12 weeks | The proportion of patients achieving tumor shrinkage meeting specified criteria and maintaining it for a defined duration, encompassing both CR and PR cases. Tumor response is evaluated according to RECIST V1.1 criteria. |
Countries
China
Outcome results
None listed