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

Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04354662
• Other study ID #: Gastrim 001
• Status: Recruiting
• Phase: Phase 2
• Start date: September 26, 2019
• Est. completion date: June 30, 2024

Study information

• Verified date: January 2021
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: Hongli Li, Dr
• Phone: 8618622221233
• Email: hongli[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 35
• Est. completion date: June 30, 2024
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Toripalimab
240mg d1
• Docetaxel
50mg/m2, d1;
• Fluorouracil
2600 mg/m², d1
• Leucovorin
200 mg/m², d1
• Oxaliplatin
85 mg/m², d1

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Adverse Events	For any adverse reactions, the researchers refer to the National Cancer Institute (NCI) standard of common toxicity (CTC)	Up to 6 months
Secondary	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
Secondary	5-year Survival Rate	Proportion of patients with resectable gastric cancer who survived 5 years after perioperative treatment	Up to 5 years