Clinical trial NCT04354662: Toripalimab Combined With FLOT Neoadjuvant Chemotherapy in Patients With Resectable Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: Gastric Cancer
Neoadjuvant Chemotherapy
Immunotherapy
Toripalimab
Pathological Remission
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, non-randomized, phase II clinical trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. locally advanced (\>T1) and/or nodal positive (N+) histologically proven adenocarcinoma of the gastric or gastroesophageal junction without distant metastases (M0)
2. no previous surgical resection
3. no previous cytostatic chemotherapy
4. Age \> 18 years, no more than 75 years (female and male)
5. Karnofsky Performance Status score of physical condition is 80-100
6. surgical resectability
7. Exclusion of peritoneal carcinomatosis (if clinically suspected) via laparoscopy
8. Leucocytes \> 4.000/µl
9. Platelets \> 100.000/µl
10. Serum creatinin ≤ 1.5x of normal value, or Creatinin-Clearance \> 50 ml/min
11. written informed consent.

Exclusion Criteria:

1. Distant metastasis or local invasion of adjacent organs;
2. Recurrent or residual gastric cancer;
3. Having or having had autoimmune disease;
4. Previous organ transplantation or HIV patients;
5. Allergy or contraindications to Toripalimab, 5- Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel;
6. Malignant secondary disease;
7. Severe non-surgical disease or acute infection;
8. Peripheral polyneuropathy \> NCI grad I;
9. Blood system, liver and kidney function were damaged;
10. Symptomatic brain metastasis;
11. Obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency and severe gravity valve disease;
12. Psychotic subjects who are not easy to control;
13. Pregnant or lactating subjects.

Primary outcomes:
measure: 3-year Disease-Free Survival Rate
timeFrame: Up to 3 years
measure: Pathological complete response rate (pCR)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Major pathological (complete and nearly complete) response (MPR)
timeFrame: Up to 6 months
measure: Adverse Events
timeFrame: Up to 6 months
measure: 5-year Disease-Free Rate
timeFrame: Up to 5 years
measure: 5-year Survival Rate
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Hongli Li, Dr
role: PRINCIPAL_INVESTIGATOR
References: