Toripalimab Combined With FLOT Neoadjuvant Chemotherapy in Patients With Resectable Gastric Cancer

Study Overview
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Brief Summary
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Gastric cancer is one of the most common malignant tumors of the digestive tract. Gastric cancer patients diagnosed for the first time in China have a higher proportion of advanced stages and a higher postoperative metastasis rate. Studies have shown that patients with good pathological response after preoperative neoadjuvant therapy (such as tumor regression grade, TRG0 or 1) have a better prognosis. The AIO-FLOT4 study found that preoperative perioperative FLOT chemotherapy not only prolonged the progression-free survival (PFS) time and overall survival (OS) time of patients with advanced gastric cancer, but also increased postoperative pathological remission rate. How to further improve the efficacy of the perioperative treatment plan may be beneficial to improve the long-term survival of gastric cancer patients. Several clinical studies have also confirmed that PD-1 antibody significantly prolongs the life of gastric cancer patients who have failed advanced chemotherapy in the back-line treatment. Thus the investigators plan to conduct this clinical trials to evaluate the safety and efficacy of Toripalimab (PD-1 antibody) combined with FLOT regimen in the perioperative period.The secondary end points included pathological remission rate, resection rate, D2 radical resection rate, 5-year disease-free survival (DFS) rate and 5-year OS rate.

Detailed Description
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Gastric cancer is one of the most common malignant tumors of the digestive tract, accounting for the second incidence of malignant tumors, and the third mortality factor related to malignant tumors. In China, most patients with gastric cancer diagnosed for the first time are already in the advanced stage, with stage II and III patients accounting for 63%, and the postoperative recurrence rate is higher. Studies have shown that patients with good pathological response after preoperative neoadjuvant therapy (such as TRG0 or 1) have a better prognosis. In recent years, the AIO-FLOT4 study have found that perioperative chemotherapy with FLOT regimen has prolonged the PFS and OS in patients with advanced gastric cancer. It is preferred to recommend perioperative chemotherapy with FLOT regimen for patients with advanced gastric cancer in the NCCN guidelines or Chinese CSCO guidelines. How to further improve the efficacy of the perioperative treatment plan may be beneficial to improve the long-term survival of gastric cancer patients. Several clinical studies have also confirmed that PD-1 antibody significantly prolongs the life of gastric cancer patients who have failed advanced chemotherapy in the back-line treatment. In the KEYNOTE-059 study, the effectiveness of chemotherapy combined with PD-1 antibody in gastric cancer patients newly treated reached 62%. It is necessary to explore the efficacy of PD-1 antibody combined with FLOT regimen in the perioperative period. Thus the investigators plan to conduct this clinical trials to evaluate the safety and efficacy of Toripalimab (PD-1 antibody) combined with FLOT regimen in the perioperative period.The secondary end points included pathological remission rate, resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate.

Official Title
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Phase II Study of Toripalimab Combined With Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Docetaxel
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: locally advanced (>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the gastric or gastroesophageal junction without distant metastases (M0) no previous surgical resection no previous cytostatic chemotherapy Age > 18 years, no more than 75 years (female and male) Karnofsky Performance Status score of physical condition is 80-100 surgical resectability Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy Leucocytes > 4.000/µl Platelets > 100.000/µl Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance > 50 ml/min written informed consent. Exclusion Criteria: Distant metastasis or local invasion of adjacent organs; Recurrent or residual gastric cancer; Having or having had autoimmune disease; Previous organ transplantation or HIV patients; Allergy or contraindications to Toripalimab, 5- Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel; Malignant secondary disease; Severe non-surgical disease or acute infection; Peripheral polyneuropathy > NCI grad I; Blood system, liver and kidney function were damaged; Symptomatic brain metastasis; Obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency and severe gravity valve disease; Psychotic subjects who are not easy to control; Pregnant or lactating subjects.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, non-randomized, phase II clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Toripalimab combined with FLOT<br>In the perioperative period, patients with resectable gastric cancer is treated with flot regimen combined with Toripalimab to observe whether the 3-year disease-free survival (DFS) rate, pathological remission rate, R0 resection rate, D2 radical resection rate, 5-year DFS rate and 5-year OS rate could be improved. | Drug: Toripalimab<br>* 240mg d1<br>* Other names: JS001;Drug: Docetaxel<br>* 50mg/m2, d1;<br>Drug: Fluorouracil<br>* 2600 mg/m², d1<br>Drug: Leucovorin<br>* 200 mg/m², d1<br>Drug: Oxaliplatin<br>* 85 mg/m², d1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Disease-Free Survival Rate | The primary end point of the study is the effect of perioperative time flot regimen combined with Toripalimab and D2 radical operation on the 3-year disease-free survival time of resectable gastric cancer. | Up to 3 years | 
| Pathological complete response rate (pCR) | Proportion of patients with gastric cancer who received Toripalimab combined with FLOT regimen after 4 cycles of neoadjuvant therapy and postoperative pathological examination TRG1a | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological (complete and nearly complete) response (MPR) | Proportion of patients with gastric cancer who received Toripalimab combined with FLOT regimen after 4 cycles of neoadjuvant therapy and postoperative pathological examination TRG1a or 1b. | Up to 6 months | 
| Adverse Events | For any adverse reactions, the researchers refer to the National Cancer Institute (NCI) standard of common toxicity (CTC) | Up to 6 months | 
| 5-year Disease-Free Rate | The proportion of patients with resectable gastric cancer who have no recurrence or metastasis after 5 years of perioperative treatment | Up to 5 years | 
| 5-year Survival Rate | Proportion of patients with resectable gastric cancer who survived 5 years after perioperative treatment | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Neoadjuvant Chemotherapy, Immunotherapy, Toripalimab, Pathological Remission