Preoperative Adjuvant SOX Plus PL-1 Antibody and FLOT Plus PD-1 Antibody for Locally Advanced dMMR Gastric Cancer

Phase 1

Recruiting

• Conditions: Chemotherapeutic Toxicity; Immune-related Adverse Event; Gastric Cancer
• Interventions: Drug: FLOT+PD-1 antibody; Drug: SOX+PD-1 antibody

• Registration Number: NCT06440811
• Lead Sponsor: Xijing Hospital

Brief Summary

The goal of the study is to learn about Safety and efficacy of preoperative adjuvant SOX regimen combined with PD-1 antibody versus FLOT Regimen with PD-1 antibody in localized deficient mismatch repair gastric cancer. The main question it aims to answer are:

* Safety and efficacy of preoperative adjuvant SOX regimen combined with PD-1 antibody versus FLOT regimen with PD-1 antibody for the treatment of localized deficient mismatch repair gastric cancer

* Disease-free survival of preoperative adjuvant SOX plus PD-1 antibody and FLOT plus PD-1 antibody for dMMR and locally advanced gastric cancer.

Participants will be divided into two groups to use a FLOT chemotherapy regimen plus PD-1 antibody and a SOX chemotherapy regimen plus PD-1 antibody.

Researchers would compare tumor regression grade, adverse effects and survival benefit of two preoperative adjuvant regimens.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-12
• Study Start: 2024-01-01
• Study First Submitted: 2024-04-06
• Study First Submitted QC: 2024-06-03
• Last Update Submitted: 2024-06-03
• Study First Posted: 2024-06-04
• Last Update Posted: 2024-06-04
• Primary Completion: 2025-01-01
• Study Completion: 2025-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• 1. Age >=18 years and <100 years.
• 2. Diagnosed with locally advanced gastric cancer.
• 3. Eastern Cooperative Oncology Group ECOG PS score 0-1.
• 4. adoption of preoperative chemotherapy treatment and PD-1 antibody therapy.
• 5. deficient mismatch repair identified by pathological detection.

Exclusion Criteria

• 1. Locally advanced unable to resect or metastatic tumors.
• 2. Patients with recurrence of residual gastric cancer
• 3. Patients refusing surgical resection after preoperative chemotherapy therapy.
• 4. Have received any anti-tumor therapy such as chemotherapy, radiotherapy, immunotherapy, etc., or have been more than 180 days since the last treatment.
• 5. Patients with confirmed allergy to the study drug and/or its excipients.
• 6. Severe malnutrition and active autoimmune diseases.
• 7. Pregnant or lactating women.
• 8. Patients with medical systemic diseases and psychiatric diseases that are not amenable to chemotherapy.
• 9. Patients with acute infections requiring antibiotic treatment.
• 10. Patients with acute infections requiring antibiotic treatment.
• 11. Patients who are concomitantly receiving other immunotherapy, corticosteroids, and other anticancer therapies during the trial.
• 12. Positive test result for hepatitis B or hepatitis C virus.
• 13. Untreated central nervous system metastatic peripheral neuropathy (>grade 1).
• 14. History of malignancy within the past 5 years (with the exception of curative, localized cancer).
• 15. Patients who are not expected to achieve R0 resection.
• 16. Weight loss greater than or equal to 20% within 4 weeks before the first dose.
• 17. Patients with multiple factors affecting oral medication.
• 18. Vaccination within 4 weeks prior to the first dose of study drug.
• 19. Patients who have received immune checkpoint inhibitors and develop serious adverse reactions after treatment and need to be permanently disabled.
• 20. The investigator believes that the subject has other serious systemic diseases or other reasons and is not suitable for this clinical study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FLOT+PD-1 antibody	FLOT+PD-1 antibody	Patients in the FLOT group received 4 cycles of standard FLOT chemotherapy, the FLOT chemotherapy cycle consists of: day 1: intravenous 5-FU 2600 mg/m² inserted through a peripherally inserted central catheter (PICC) for 24 hours intravenous folic acid 200 mg/m2 intravenous OXA 85 mg/m² intravenous TXT 50 mg/m². The next cycle of chemotherapy was repeated on day 15. PD-1 antibody: 360 mg every 3 weeks.
SOX+PD-1 antibody	SOX+PD-1 antibody	Patients in the SOX group received 3 cycles of S-1 + OXA chemotherapy prior to radical gastrectomy.The SOX chemotherapy cycle consists of: day 1: intravenous OXA 130 mg/m² days 1-14: oral S-1 80 mg/m², 2 times/Day. Repeat next chemotherapy on day 22. PD-1 antibody: 360 mg every 3 weeks.

Primary Outcome Measures

Name	Time	Method
adverse event	From the preoperative chemotherapy until the occurrence of adverse events, assessed up to 180 days	adverse event caused by FLOT, SOX or PD-1 antibody treatment, which were coded using the Medical Dictionary Regulatory Activities version 20.1 and adverse event grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events

Secondary Outcome Measures

Name	Time	Method
tumor regression grade	From the surgery to evaluation of tumor regression grade, assessed up to 1 week	Residual tumor components in post-radiotherapy samples and the proportion of fibrosis
objective response rate	From the surgery to evaluation of objective response rate, assessed up to 1 week	objective response rate defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST).
Duration of response	From the first assessment of the tumor as CR or PR to the first assessment of PD (Progressive Disease) or death from any cause, assessed up to 120 months.	Duration of response
disease-free survival	From date of diagnosis until the first documented recurrence or death, assessed up to 120 months	from diagnosis to recurrence or death

Trial Locations

Locations (3)

Xijing hospital; 🇨🇳 Xi'an, Shaanxi, China

Tangdu hospital; 🇨🇳 Xi'an, Shaanxi, China

Shaanxi Provincial People's Hospital; 🇨🇳 Xi'an, Shaanxi, China