The Safety and Efficacy of Neoadjuvant Immunochemotherapy Followed by Laparoscopic Gastrectomy for Gastric Cancer

The Safety and Efficacy of Neoadjuvant Immunochemotherapy Followed by Laparoscopic Gastrectomy for Gastric Cancer: A Multicenter Real-world Clinical Study

To evaluate the safety and effectiveness of laparoscopic gastrectomy (LG) following neoadjuvant immunochemotherapy (nICT)

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced Gastric Cancer
• Intervention / Treatment: Drug: immune checkpoint inhibitors: sintilimab, nivolumab, and camrelizumab

Detailed Description

comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups.

• Study Type: Observational
• Enrollment (Actual): 585

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients with locally advanced gastric cancer who underwent neoadjuvant therapy

Description

Inclusion Criteria:

• Age: 18-85 years of age
• Gastric adenocarcinoma was confirmed by pathology# including histology or cytology##
• CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.
• measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.#CT scan of tumor lesion length≥10mm#CT scan short diameter≥15mm#scan slice thicknes 5mm#
• ECOG#Eastern Cooperative Oncology Group#PS#Performance Status#:0-1 scores;
• the expected survival time is more than 12 weeks

• the main organ function is normal, which should meet the following criteria:

  (1) blood routine examination standards should be met#no blood transfusion within 14 days#

  a#HB≥ 100g/L b. WBC≥3×109/L c. ANC≥1.5×109/L d. PLT≥100×109/L #2#biochemical examination shall comply with the following criteria#

  1. BIL#1.5 normal upper limit ULN
  2. ALT and AST#2.5 ULN,GPT≤1.5×ULN
  3. Cr≤1 ULN#CCR#creatinine clearance rate#60ml/min(Cockcroft Gault formula)
• women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug test; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug test#
• No other clinical studies were conducted before and during the treatment
• participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up.

Exclusion Criteria:

• Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy
• Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for larger abdominal surgery
• patients with metastasis
• Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin
• A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation
• Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection
• pregnant or lactating women
• The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg)
• With # magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency
• Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and unresected gastric primary tumor; patients with the risk of bleeding should take the gastroscopy test, if it is the gastric cancer, and researchers believe that may results in massive digestive tract hemorrhage#coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;
• Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure (2) above unstable angina pectoris (3) occurred within 1 year (4) have clinical significance of myocardial infarction (mi) room sex or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled
• History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia
• Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g);
• A person who has previously been allergic to any component of camrilizumab or to any component of the drug under study
• The researchers consider those who were not suitable for inclusion.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
neoadjuvant immunochemotherapy group; The immune checkpoint inhibitors (ICIs) used for neoadjuvant immunotherapy in this study included sintilimab, nivolumab, and camrelizumab. Neoadjuvant chemotherapy regimens were primarily categorized into two- and three-agent regimens. The two-agent regimens included: SOX (S-1 + oxaliplatin), CapeOx (capecitabine + oxaliplatin), AS (S-1 + nab-paclitaxel), FOLFOX (oxaliplatin + fluorouracil) and DS (S-1 + docetaxel). The three-agent regimens included: FLOT (docetaxel + oxaliplatin + fluorouracil), DOS (docetaxel + oxaliplatin + S-1) and POF (paclitaxel + oxaliplatin + fluorouracil). Dosages were calculated based on drug monographs, guidelines, and patient body surface area. The patients underwent LG within 4-6 weeks after completing neoadjuvant therapy.	Drug: immune checkpoint inhibitors: sintilimab, nivolumab, and camrelizumab; Drug: Sintilimab, Nivolumab, and Camrelizumab，One course will last 21 days.Given once every 3 weeks at a dose of 200 mg. Drug: nab-paclitaxel nab-paclitaxel one course will last 21 days#Given twice every 3 weeks at a dose of 125 mg/m2. Drug:oxaliplatin Oxaliplatin one course will last 21 days#Given once every 3 weeks at a dose of 130 mg/m2. Drug:docetaxel docetaxel one course will last 21 days#Given once every 3 weeks at a dose of 40mg/m2. Drug:fluorouracil fluorouracil one course will last 14 days#Given once every 2 weeks at a dose of 2800mg/m2. Drug: Capecitabine Capecitabine was calculated according to body surface area every 3 weeks at a dose of 1000 mg/m2, P.O., bid, d1-d14 Drug: S1 S-1 was calculated according to body surface area, P.O., bid, d1-d14#And the dosage according body surface area:<1.25m2, 40mg everytime;1.25-1.5m2,50mg every time; >1.5m2, 60mg every time
neoadjuvant chemotherapy group; Neoadjuvant chemotherapy regimens were primarily categorized into two- and three-agent regimens. The two-agent regimens included: SOX (S-1 + oxaliplatin), CapeOx (capecitabine + oxaliplatin), AS (S-1 + nab-paclitaxel), FOLFOX (oxaliplatin + fluorouracil) and DS (S-1 + docetaxel). The three-agent regimens included: FLOT (docetaxel + oxaliplatin + fluorouracil), DOS (docetaxel + oxaliplatin + S-1) and POF (paclitaxel + oxaliplatin + fluorouracil). Dosages were calculated based on drug monographs, guidelines, and patient body surface area. The patients underwent LG within 4-6 weeks after completing neoadjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathological complete response	pathological complete response (pCR)	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major pathological response	major pathological response#MPR	4 months

Collaborators and Investigators

• Sponsor: Fujian Medical University
• Investigators: Principal Investigator: Chang-Ming Huang, Fujian Medical University Union Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 30, 2022
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Nivolumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2023KY160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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