SOX Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of HER2-positive Locally Advanced Gastric Adenocarcinoma

Phase 2

Not yet recruiting

• Conditions: Sintilimab; Gastric or Gastroesophageal Junction Adenocarcinoma; Locally Advanced Solid Tumor; S-1; HER2-positive; Immunotherapy; Oxaliplatin
• Interventions: Drug: sintilimab; Drug: Trastuzumab; Drug: S-1 plus oxaliplatin

• Registration Number: NCT05218148
• Lead Sponsor: Aiping Zhou

Brief Summary

The SOX regimen has became the standard perioperative chemotherapy for locally advanced gastric cancer; The immune checkpoint inhibitors have become a standard treatment for advanced or metastatic gastric cancer；For HER2-positive locally advanced gastric cancer, some phase II studies have shown that chemotherapy combined with trastuzumab can further improve the pathological remission rate;This prospective phase II clinical trial was designed, using SOX combined with sintilimab and trastuzumab to treat HER2 positive locally advanced gastric or gastroesophageal junction adenocarcinoma patients.

Detailed Description

This phase II trial is a single-arm and single-center clinical study. Neoadjuvant chemotherapy is a standard treatment for locally advanced gastric cancer. The SOX regimen has became the standard perioperative chemotherapy regimen for locally advanced gastric cancer. For HER2-positive locally advanced gastric cancer, the neoadjuvant treatment is still based on chemotherapy alone. Some phase II studies have shown that chemotherapy combined with trastuzumab can further improve the pathological response. But it has not yet become a standard treatment strategy.

In the field of gastric cancer, checkpoint inhibitors have become a standard treatment for advanced or metastatic gastric cancer. PD-1 monoclonal antibody (Sintilimab) + trastuzumab + chemotherapy (SOX regimen ) may be an ideal perioperative treatment for HER2-positive locally advanced gastric cancer.

Study Timeline

• Study First Submitted: 2022-01-16
• Study First Submitted QC: 2022-01-28
• Study First Posted: 2022-02-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-28
• Study Start: 2022-04-01
• Last Update Posted: 2022-04-06
• Primary Completion: 2024-10-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Sign the informed consent form.
• Locally advanced adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II/III) confirmed by pathology or cytology.
• The definition of a positive HER2 test result is as follows: IHC detects HER2 3+ or IHC detects HER2 2+ and FISH is positive.
• Clinically, based on chest, abdomen and pelvic CT, gastroscopy, endoscopic ultrasonography, gastrointestinal contrast, ordinary ultrasound, or laparoscopy if possible, it is judged as T3-4a N+ or T4bN any gastric cancer or gastroesophageal junction cancer (refer to AJCC Article Version 8 in stages).
• Patients have not received chemotherapy and/or immunotherapy and/or trastuzumab treatment and/or radiotherapy in the past.
• Age 18-75 years old.
• The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1, and there was no deterioration within 2 weeks before the first administration of the study drug.
• Good organ function:

Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×109/L, neutrophil ≥1.5×109/L, platelet ≥100×109/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL.

Exclusion Criteria

• The pathology is other types besides adenocarcinoma, such as squamous cell carcinoma, adenosquamous carcinoma, neuroendocrine carcinoma and so on.
• Have received chemotherapy and/or radiotherapy in the past.
• Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies and other immunotherapy in the past.
• Have received any anti-HER2 therapy in the past.
• Intra-abdominal dissemination or distant metastasis (M1).
• Clinically significant ascites.
• Known to have allergic reactions to oxaliplatin and any ingredients or excipients of Tiggio.
• Known to have allergic reactions to any ingredients or excipients of Sintilimab and Trastuzumab.
• Inability to swallow, intestinal obstruction, or other factors that affect the administration and absorption of the drug.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	S-1 plus oxaliplatin	Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery
Group B	S-1 plus oxaliplatin	Group B: SOX regimen, 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery
Group A	sintilimab	Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery
Group A	Trastuzumab	Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery

Primary Outcome Measures

Name	Time	Method
Major pathological response rate (MPR)	Up to 6 months	Proportion of subjects with residual tumor less than 10% or complete response

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	Up to 3 years	Proportion of subjects with initial RECIST 1.1 measurable disease who have complete response (CR) or partial response (PR) according to iRECIST
Incicende of Adverse Events (AEs)	Up to3 years	Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE) assessed by CTCAE v5.0.
Disease-free survival (DFS)	Up to 3 years	Time from Cycle 1 Day 1 treatment administration to the first documented event of: disease progression, disease recurrence following surgery (preferably biopsy proven), or death - whichever occurs first.
Pathological response rate (refer to Becker-TRG evaluation standard)	Up to 3 years	TRG level 1-3: 1a: No tumor remains at all; 1b: Less than 10% of the tumor remains 2: 10%-50% tumor residual 3: More than 50% of the tumor remains or there is no change in the tumor
Overall survival (OS)	Up to 3 years	Time from Cycle 1 Day 1 treatment administration to death due to any cause.
Biomarker assessment	Up to3 years	To analyze the differences of gene and immune microenvironment biomarkers among patients with different curative effects, and further explore the relationship with the efficacy of clinical treatment.; To analyze the correlation between peripheral blood indexes and the efficacy of clinical treatment.

Trial Locations

Locations (1)

Cancer Hospital & Institute, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China