Toripalimab Plus FLOT in Locally Advanced Gastric Cancer

NCT ID: NCT04891016

Last Updated: 2024-06-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-25
• Study Completion Date: 2028-12-31

Brief Summary

Neoadjuvant chemoimmunotherapy for locally advanced gastric and gastroesophageal junction (G/GEJ) cancer is currently under investigation. Most clinical studies have simply combined chemotherapy with anti-PD-1 therapy without considering the impact of chemotherapy drugs on activated immune cells. We designed this study to explore two different treatment regimens for neoadjuvant chemotherapy in patients with locally advanced G/GEJ cancer. One group received FLOT plus toripalimab on Day 1 of each cycle, every 2 weeks for 4 cycles, followed by surgery; the other group received FLOT plus toripalimab on Day 3 of each cycle, every 3 weeks for 3 cycles, followed by surgery. A total of 69 subjects were enrolled. Preliminary statistical analysis conducted one year after the last subject was enrolled revealed no statistically significant differences in pCR and MPR between the two regimens. The median DFS for both groups has not been reached, and there is no statistically significant difference in DFS between the two groups at present. Further subgroup analysis indicated that among subjects with PD-L1 CPS ≥1, the triweekly group achieved a rate of 42.1%, compared to 29.4% in the biweekly group, with no statistically significant difference between the two groups. However, the incidence of bone marrow suppression was lower in the triweekly group than in the biweekly group. Based on the preliminary findings, we plan to conduct an expanded study and transition to a multicenter clinical trial. This study aims to further validate the efficacy of the triweekly chemoimmunotherapy in patients with PD-L1 CPS ≥1 locally advanced G/GEJ cancer.

Detailed Description

Eligible patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.

Conditions

Chemotherapy; Immune Checkpoint Inhibitor; Locally Advanced Gastric Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

experimental group

patients received FLOT regimen on day 1 and toripalimab on day 3.

Group Type: EXPERIMENTAL

FLOT combined with toripalimab

Intervention Type: DRUG

Patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.

Interventions

FLOT combined with toripalimab

Patients received FLOT combined with toripalimab on Day 3 every 3 weeks, for a total of 3 cycles, followed by surgical treatment. Postoperative adjuvant therapy was determined based on pathological results: if a pathological complete response (pCR) was achieved, patients received 2 additional cycles of the neoadjuvant regimen; if pCR was not achieved, patients were given 4 cycles of SOX combined with toripalimab postoperatively.

Intervention Type: DRUG

Other Intervention Names

FLOT plus toripalimab

Eligibility Criteria

Inclusion Criteria

• 70 ≥ Age ≥ 18 years regardless of gender
• Gastric adenocarcinoma confirmed by pathology
• no distant metastasis and resectable or potentially resectable evaluated by general surgery experts
• ECOG PS 0-1
• clinical stage T3/4 or N+ by AJCC 8.0
• PD-L1 CPS ≥1 (IHC 22C3 pharm Dx assay (Dako))
• expected lifespan over 3 months
• Adequate organ function: 1) without growth factor and blood component support in the first 2 weeks of enrollment; 2) Cardiac function: no heart disease or coronary heart disease, grade 1-2; 3) liver function: TBIL ≤ 2ULN, AST ≤ 2.5 ULN, alt ≤ 2.5 ULNX 4 Renal function: cr ≤ 1.25ULN, liver function: TBIL ≤ 2ULN, TBIL ≤ 2.5ULN, alt ≤ 2.5ULN, 4)renal function: cr ≤ 1.25ULN.
• blood pressure normal or controlled within the normal range by antihypertensive drugs
• Diabetic patients were treated with hypoglycemic drugs to control fasting blood glucose ≤ 8mmol/L
• Patients with positive hepatitis B surface antigen need to be tested for quantitative detection of hepatitis B DNA virus. HBV DNA should be less than the upper limit of the normal test value for patients with HBV infection.
• no other serious diseases conflicting with this study
• No history of other malignant tumors
• Women of childbearing age must be tested negative for blood pregnancy test within 7 days before enrollment, and subjects of childbearing age must use appropriate contraceptive measures during the trial and within 6 months after the trial
• agreement to participate in this study and signed the informed consent form

Exclusion Criteria

• Pregnant or lactating women
• Suffered from severe infectious diseases within 4 weeks before entering the group
• Bronchial asthma requires intermittent use of bronchodilators or medical intervention
• Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg/, the oral dose of prednisone lasted for more than 2 weeks
• Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction < 50%, stroke within 6 months
• Allergic to any experimental drug and its excipients, or have a history of severe allergy, or are contraindications to experimental drugs
• Severe mental disorders
• Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s Fib < 1.5g/L), bleeding tendency or undergoing thrombolysis or anticoagulation therapy
• Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, severe impairment of lung function, etc.
• Unable to swallow research drugs, chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction affect drug use and absorption
• Have a history of immunodeficiency, including positive for HIV, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplant
• Other researchers evaluate those who do not meet the criteria for admission

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Quanli Gao

Head of immunotherapy department, Clinical professor, Leader of immunotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Quanli Gao, M.D

Role: PRINCIPAL_INVESTIGATOR

Department of Immunotherapy, Henan Provincial Cancer Hospital

Locations

Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Quanli Gao, M.D

Role: CONTACT

gaoquanli2015@126.com

+8637165587483

Lingdi Zhao, M.D

Role: CONTACT

lingdizhao@126.com

+8637165587483

Facility Contacts

Quanli Gao, M.D

Role: primary

gaoquanli2015@126.com

+86-371-65587795

Lingdi Zhao, M.D

Role: backup

lingdizhao@126.com

+86-371-65587483

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Other Identifiers

HenanCH immunotherapy006

Identifier Type: -

Identifier Source: org_study_id