Study Evaluating Neoadjuvant Immunotherapy Increasing CD8+ Cell Infiltration in Advance Gastric Adenocarcinoma

Study Evaluating Neoadjuvant Immunotherapy Increasing CD8+ Cell Infiltration in Advance Gastric Adenocarcinoma : a Single Randomized Controlled Trial

Focusing on the clinical question of whether patients with advanced gastric cancer can benefit from immunotherapy, this project intends to detect the degree of CD8+ tumor-infiltrating lymphocyte infiltration in patients with advanced gastric cancer before and after receiving neoadjuvant combined immunotherapy and neoadjuvant therapy alone. To explore the evolving nature of tumor immune response before and after neoadjuvant therapy for gastric cancer, and quantitatively present it through chemical immunohistochemical techniques to achieve a more accurate diagnosis and treatment and improve the long-term efficacy of patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Gastric Carcinoma; Neoadjuvant Immunotherapy; CD8+ Tumor Infiltrating Lymphocytes
• Intervention / Treatment: Combination product: radical surgery after neoadjuvant immunotherapy; Combination product: radical surgery after neoadjuvant chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Participation Criteria

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. Age from 18 to 75 years
2. Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically ；
3. CT/MRI, PET-CT, or laparoscopic exploration should be performed before surgery to confirm the diagnosis of stage ≥cT2 or N+；
4. Patients who have not received other treatments such as surgery, radiotherapy, chemotherapy, targeted therapy or immunotherapy；
5. Performance status of 0 or 2 on Eastern Cooperative Oncology Group scale (ECOG)；
6. Estimated survival time was over 3 months；
7. No serious heart, lung and liver dysfunction; no jaundice and gastrointestinal obstruction; no acute infection;；
8. The major organs are functioning normally and meet the following criteria:

(1) Blood routine examination should meet the requirements (no blood transfusion within 14 days):

1. HB≥100g/L，
2. WBC≥3×109/L
3. ANC≥1.5×109/L，
4. PLT≥100×109/L； （2）Biochemical tests must meet the following criteria：

a. BIL <1.5×upper limit of normal (ULN)， b. ALT and AST<2.5ULN，GPT≤1.5×ULN； c. Cr≤1ULN，Ccr >60ml/min 9. Fertile women must have taken a pregnancy test (serum) within 7 days prior to enrollment with negative results and be willing to use an appropriate method of contraception during the trial period and 8 weeks after the last trial drug; For men, they should be surgically sterilized or agree to use the appropriate method of contraception during the trial period and 8 weeks after the last administration of the trial drug 10. Did not participate in other clinical studies before and during treatment 11. Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up

Exclusion Criteria:

1. History of other malignant disease within past five years；
2. History of immunodeficiency, including HIV positive, or other acquired congenital immunodeficiency disease, or a history of organ transplantation and allogeneic bone marrow transplantation；
3. Contraindications to surgery and chemotherapy, or whose physical condition and organ function do not allow for major abdominal surgery
4. Distant metastases；
5. Accompanied by severe heart, lung, liver and kidney diseases; neurological and mental diseases; jaundice and accompanied by severe infection；
6. Women during pregnancy or breast-feeding；
7. Patients with high blood pressure that cannot be reduced to the normal range after antihypertensive drug treatment (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg);
8. Suffering from coronary heart disease of grade I or above, arrhythmia (including QTc interval prolongation > 450 ms in men and > 470 ms in women), and cardiac insufficiency;
9. Patients with a clear tendency to gastrointestinal bleeding, including the following conditions: patients with locally active ulcer lesions, fecal occult blood (++), and history of melena and hematemesis within 2 months; patients with abnormal coagulation function (INR> 1.5, APTT>1.5 ULN);
10. Patients with a history of cardiovascular and cerebrovascular diseases who are still taking oral thrombolytics or anticoagulants;
11. Patients with positive urine protein (urinary protein test 2+ or above, or 24-hour urine protein quantitative> 1.0g;
12. Multiple factors affect oral drugs (such as inability to swallow, persistent uncontrollable nausea and vomiting, chronic diarrhea and intestinal obstruction, etc.);
13. Those who have allergic reactions to the drugs in this study;
14. The researcher believes that it is not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: radical surgery after neoadjuvant immunotherapy (albumin Paclitaxel + Seggio + PD-1 inhibitor); After randomization, patients received radical surgery after the neoadjuvant immunotherapy (albumin Paclitaxel + Seggio + PD-1 inhibitor)	Combination product: radical surgery after neoadjuvant immunotherapy; A total or distal gastrectomy with D2 lymph node dissection was done depending on the tumor location after neoadjuvant immunotherapy.
Active Comparator: radical surgery after neoadjuvant chemotherapy (albumin Paclitaxel + Seggio); After randomization, patients received radical surgery after neoadjuvant chemotherapy (albumin Paclitaxel + Seggio)	Combination product: radical surgery after neoadjuvant chemotherapy; A total or distal gastrectomy with D2 lymph node dissection was done depending on the tumor location after neoadjuvant immunotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of CD8+ tumor-infiltrating lymphocytes in tumor tissue and adjacent tissue before and after treatment	Changes in the number of CD8+ tumor-infiltrating lymphocytes in the tumor and adjacent tissues of the experimental group before and after the surgery compared with the control group.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from study entry to death from any cause.	2 years
Disease-free survival (DFS)	Time from study entry to disease recurrence or patient death due to disease progression	2 years
Objective response rate (ORR)	Complete response (CR) + partial response (PR)	6 months
Therapeutic drug safety	Adverse events (AEs), serious adverse events (SAEs), drug-related AEs, SAEs, and class-specific AEs (eg, hypertension, proteinuria, and hand-foot syndrome)	6 months
Surgical safety	R0 resection rate, operative mortality, surgical complications (bleeding, anastomotic leakage, incision infection), reoperation rate, hospital stay, etc.	6 months

Collaborators and Investigators

• Sponsor: Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2027

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: February 26, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 26, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma
• Other Study ID Numbers: FUGES-025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No