Perioperative Chemoimmunotherapy With/Without Preoperative Chemoradiation for Locally Advanced Gastric Cancer

NCT05161572 | Terminated Phase 2

• 1 other identifier: FDRT- LAGCCS004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

NeoRacing is a randomized phase II trial carried out at Fudan University Shanghai Cancer Center (FUSCC) in China. The study can be divided into the screening stage, treatment stage and follow-up stage. The enrolled patients will receive perioperative SOX chemotherapy, PD-1 antibody (sintilimab) and radical surgery, with or without preoperative CRT. The patients were randomized by stratified permutated block randomization on a web-based system . The status of peritoneal cytological examination (CY0 vs. CY1) was the stratification factor. The study protocol was approved by the Ethics Committee of FUSCC. All patients provided written informed consent before recruitment. Monitoring will be carried out in this tri

Conditions

Stomach Neoplasms; Esophagogastric Junction Disorder; Neoadjuvant Therapy; Chemoradiotherapy; Immunotherapy; Gastrectomy; Adenocarcinoma; Adjuvant Therapy

Keywords

Locally advanced gastric cancer; Gastroesophageal junction adenocarcinoma; Perioperative chemotherapy; Preoperative chemoradiation; PD-1 antibody

Outcome Measures

Primary Outcomes (1)

• Pathological complete regression (pCR) rate

  The primary endpoint is the pathological complete regression (pCR) rate: the proportion of patients who achieve pCR after preoperative therapy. Patients with a CY0 status at the time of enrollment should have no residual tumor cells in the primary lesion and in the dissected lymph nodes in the surgical specimens (ypT0N0M0). Patients with a CY1 status at the time of enrollment should reach both ypT0N0M0 and a CY0 status.

  6 months after the enrollment of the last subject

Secondary Outcomes (7)

• Pathological response rate (pRR)

  6 months after the enrollment of the last subject

• R0 resection rate

  6 months after the enrollment of the last subject

• Objective response rate (ORR)

  6 months after the recruitment of the last subject.

• Event-free survival (EFS)

  36 months after the recruitment of the last subject.

• Overall survival (OS)

  36 months after the recruitment of the last subject.

Other Outcomes (4)

• To study the association of baseline PD-L1 CPS, TMB, MSI/MMR status, and EBER status on the efficacy of immunotherapy.

  36 months after the recruitment of the last subject.

• To study the association between gut microbiota and the efficacy of immunotherapy.

  36 months after the recruitment of the last subject.

• To study the association between the Helicobacter pylori infection status and the efficacy of immunotherapy.

  36 months after the recruitment of the last subject.

Study Arms (2)

Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

EXPERIMENTAL

In this arm, patients will receive preoperative chemoradiotherapy (45Gy/25Fractions), two cycles of SOX and three cycles of PD-1 antibody, followed by D2 surgery and three more cycles of SOX and PD-1 antibody. Then PD-1 antibody will be given until one year after surgery.

Drug: Oxaliplatin; Drug: Tegafur-Gimeracil-Oteracil; Drug: Sintilimab; Radiation: Concurrent chemoradiation; Procedure: D2/R0 gastrectomy

Perioperative chemotherapy plus PD-1 antibody

EXPERIMENTAL

In this arm, patients will receive three cycles of SOX and PD-1 antibody, followed by D2 surgery and three more cycles of SOX and PD-1 antibody. Then PD-1 antibody will be given until one year after surgery.

Drug: Oxaliplatin; Drug: Tegafur-Gimeracil-Oteracil; Drug: Sintilimab; Procedure: D2/R0 gastrectomy

Interventions

Oxaliplatin DRUG

The SOX regimen consists of S-1 and oxaliplatin and is repeated every three weeks. Oxaliplatin will be administered intravenously at 130 mg/m2 on day 1.

Perioperative chemotherapy plus PD-1 antibody; Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

Tegafur-Gimeracil-Oteracil DRUG

The SOX regimen consists of S-1 and oxaliplatin and is repeated every three weeks. S-1 is administered orally at 40-60 mg twice a day for 14 consecutive days. Then, the patients will have a one-week rest period. The dose of S-1 is according to the body-surface area (BSA): patients with a BSA of less than 1.25 m2 receive 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 receive 100 mg daily; and those with a BSA of 1.5 m2 or more receive 120 mg daily.

Perioperative chemotherapy plus PD-1 antibody; Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

Sintilimab DRUG

The immunotherapy includes perioperative treatment and postoperative maintenance treatment. The PD-1 mAb used will be sintilimab, and the dose is 200 mg intravenously every three weeks. Regardless of which arm, the courses of immunotherapy that will be received by the enrolled patients are the same: 3 times preoperatively, 3 times postoperatively, and then maintained until one year after surgery.

Perioperative chemotherapy plus PD-1 antibody; Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

Concurrent chemoradiation RADIATION

The radiotherapy (RT) consists of 45 Gy delivered in 25 fractions every five days per week for five weeks. The dose of concurrent ChT is 60 mg/m2 S-1 orally, oral tablets twice daily, days 1-5 of each week.

Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

D2/R0 gastrectomy PROCEDURE

Gastrectomy with standard D2 lymphadenectomy is recommended. The type of gastrectomy performed depends on the location and extent of the primary lesion. For GEJ or upper third tumors, a 3 cm esophageal margin is recommended, and a total gastrectomy or esophagogastrectomy is performed. For middle third tumors, the gastric margin is recommended to be more than 5 cm, and a total gastrectomy is performed. For lower third tumors, a 2 cm duodenal margin is recommended, and a subtotal or total gastrectomy is performed. Billroth I or Roux-en-Y gastrojejunostomy is performed for distal gastrectomy patients. Roux-en-Y esophagojejunostomy is performed for patients receiving total gastrectomy.

Perioperative chemotherapy plus PD-1 antibody; Perioperative chemotherapy plus PD-1 antibody plus preoperative chemoradiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed gastric adenocarcinoma (G) or gastroesophageal junction adenocarcinoma (GEJ, excluding Siewert type I).
• The clinical stage of the enrolled patients was cT3-4aN+M0 or cT4bNanyM0. Patients with a CY1 status but no other distant metastasis were allowed for patient recruitment. The clinical stage of CY1 patients is cT3-4aN+M1 (CY1 only) or cT4bNanyM1 (CY1 only) (the 8th AJCC staging system of GC).
• The tumor was considered to be potentially resectable, which was verified by a multidisciplinary team including a surgical investigator.
• At least one evaluable lesion on abdominal CT/MRI according to the RESIST 1.1 protocol is required.
• An ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
• The patient's physical state and organ function can tolerate the planned treatment of the study protocol, including perioperative chemotherapy with the SOX regimen and immunotherapy with PD-1 monoclonal antibody, preoperative concurrent chemoradiotherapy (45 Gy/25 fractions/S-1), and major abdominal surgery.
• The baseline laboratory examinations of the patients met the following criteria:
• An adequate hematological function: an absolute neutrophil count (ANC) ≥ 1.5×109/L; a platelet count ≥ 100×109/L; a hemoglobin level ≥ 90 g/L.
• Adequate liver function: total bilirubin ≤ 1.5×upper limit of normal (ULN); AST/ALT \< 2.5×ULN; ALP ≤ 2.5×ULN; ALB ≥ 30 g/L.
• Adequate renal function: serum creatinine ≤ 1.5 × ULN; creatinine clearance rate ≥ 60 ml/min.
• Adequate coagulation function: INR/PT ≤ 1.5×ULN; APTT ≤ 1.5×ULN.
• There was no serious concomitant disease, and the patient's life expectancy was more than 6 months.
• Male or female. Age ≥ 18 years and ≤ 75 years.
• Patients agreed to sign a written informed consent before recruitment.
• Patients had good compliance with the study procedures, including laboratory examinations, auxiliary examinations and treatment.

You may not qualify if:

• Clinical or histopathological evidence of peritoneal seeding (P1) or distant metastasis (M1).
• Patients who have previously received surgery, chemotherapy, radiotherapy or immunotherapy for gastric cancer.
• Patients had a history of cancer in the five years before randomization except for squamous or basal cell carcinoma of the skin that had been effectively treated and superficial bladder cancer, cervical carcinoma in situ and breast cancer in situ that had been treated by surgery.
• Pregnant or lactating females or planning to become pregnant or lactating.
• History of allergy to any drugs involved in this study.
• History of allogeneic stem cell transplantation or organ transplantation.
• Vaccinated with a live vaccine within 4 weeks before recruitment.
• History of anti-PD-1, PD-L1, PD-L2 or any other specific T cell costimulation or checkpoint pathway targeted therapy.
• History of using steroids (dose \> 10 mg/d prednisone) or other systemic immunosuppressive therapy within 14 days before recruitment, except for patients treated with the following regimen: steroids used for hormone replacement (dose \> 10 mg/d prednisone); local application of steroids with little systemic absorption; short-term (≤ 7 days) use of steroids to prevent allergy or vomiting.
• Patients with weight loss of more than 20% within 2 months before recruitment.
• Uncontrolled systemic diseases, including diabetes and hypertension.
• Failure of important organs (heart, lung, liver, kidney, etc.).
• Moderate or severe renal injury \[creatinine clearance ≤ 50 ml/min (according to Cockroft \& Gault equation)\] or SCR \> ULN.
• Dipyrimidine dehydrogenase (DPD) deficiency.
• Patients with central nervous system (CNS) disorders, peripheral nervous system disorders or psychiatric diseases.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Related Publications (17)

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MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma

Interventions

Oxaliplatin; tegafur-gimeracil-oteracil; sintilimab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the department of radiation oncology

Study Record Dates

• First Submitted: November 21, 2021
• First Posted: December 17, 2021
• Study Start: September 28, 2021
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)