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

February 16, 2021 updated by: Tianjin Medical University Cancer Institute and Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Hongli Li, Dr
  • Phone Number: 8618622221233
  • Email: hongli@126.com

Study Contact Backup

  • Name: Jinyu Deng, Dr
  • Phone Number: 8618622228656

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:
          • Shaohua Ge, Dr
          • Phone Number: 1051 8602223340123
          • Email: hongli@126.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Toripalimab combined with FLOT
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
240mg d1
Other Names:
  • JS001
Drug: Docetaxel
50mg/m2, d1;
Drug: Fluorouracil
2600 mg/m², d1
Drug: Leucovorin
200 mg/m², d1
Drug: Oxaliplatin
85 mg/m², d1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-year Disease-Free Survival Rate
Time Frame: Up to 3 years
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)
Time Frame: Up to 6 months
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)
Time Frame: Up to 6 months
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
Time Frame: Up to 6 months
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
Time Frame: Up to 5 years
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
Time Frame: Up to 5 years
Proportion of patients with resectable gastric cancer who survived 5 years after perioperative treatment
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tianjin Medical University Cancer Institute and Hospital

Investigators

  • Principal Investigator: Hongli Li, Dr, Tianjin Medical University Cancer Institute & Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 26, 2019

Primary Completion (ANTICIPATED)

March 31, 2022

Study Completion (ANTICIPATED)

June 30, 2024

Study Registration Dates

First Submitted

April 15, 2020

First Submitted That Met QC Criteria

April 19, 2020

First Posted (ACTUAL)

April 21, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 18, 2021

Last Update Submitted That Met QC Criteria

February 16, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Gastrim 001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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