Clinical trial NCT05218148: SOX Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of HER2-positive Locally Advanced Gastric Adenocarcinoma
Official title: Phase II Clinical Study of Oxaliplatin Plus S-1 (SOX) Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of Locally Advanced HER2-positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HER2-positive
Locally Advanced Solid Tumor
Immunotherapy
Sintilimab
S-1
Oxaliplatin
Gastric or Gastroesophageal Junction Adenocarcinoma
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2022-02-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is an open-label, randomized controlled, exploratory phase II study. Patients with HER2-positive locally advanced gastric or gastroesophageal junction adenocarcinoma who have not received any anti-tumor therapy were randomized in a 1:1 ratio to receive preoperatively: Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Major pathological response rate (MPR)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Pathological response rate (refer to Becker-TRG evaluation standard)
timeFrame: Up to 3 years
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
measure: Disease-free survival (DFS)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Incicende of Adverse Events (AEs)
timeFrame: Up to3 years
measure: Biomarker assessment
timeFrame: Up to3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital & Institute, Chinese Academy of Medical Sciences
Study officials:
References: