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

NCT05218148 | Unknown Phase 2

• 1 other identifier: NCC-008261
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

HER2-positive; Locally Advanced Solid Tumor; Immunotherapy; Sintilimab; S-1; Oxaliplatin; Gastric or Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Major pathological response rate (MPR)

  Proportion of subjects with residual tumor less than 10% or complete response

  Up to 6 months

Secondary Outcomes (6)

• Pathological response rate (refer to Becker-TRG evaluation standard)

  Up to 3 years

• Objective response rate (ORR)

  Up to 3 years

• Disease-free survival (DFS)

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

• Incicende of Adverse Events (AEs)

  Up to3 years

Study Arms (2)

Group A

EXPERIMENTAL

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

Drug: sintilimab; Drug: Trastuzumab; Drug: S-1 plus oxaliplatin

Group B

ACTIVE COMPARATOR

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

Drug: S-1 plus oxaliplatin

Interventions

sintilimab DRUG

Sintilimab 200mg was administered as a 30-60 min intravenous (IV) infusion every 3 weeks.3 cycles before surgery and 5 cycles after surgery.

Group A

Trastuzumab DRUG

Trastuzumab was 8mg/kg for the first time, and 6mg/kg for the follow-up. 3 cycles before surgery and 5 cycles after surgery.

Group A

S-1 plus oxaliplatin DRUG

Oxaliplatin 130 mg/m2 was administered IV every 3 weeks. S-1 was given orally twice daily for the first 2 weeks of each 3-week cycle. The S-1 dose was 40 mg for body surface area (BSA) \< 1.25 m2, 50 mg for BSA 1.25 to \<1.5 m2 and 60 mg for BSA ≥1.5 m2. Body surface area \&lt;1.25m2: Tegio 40mg bid day 1 \~ 14; Body surface area 1.25 \~ \&lt;1.5m2: Tegio 50mg bid day 1 \~ 14; Body surface area ≥1.5m2: Tegio 60mg bid day 1 \~ 14; 3 cycles before surgery and 3 cycles after surgery.

Group A; Group B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aiping Zhou: lead

Study Sites (1)

Cancer Hospital & Institute, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

MeSH Terms

Interventions

sintilimab; Trastuzumab; S 1 (combination); Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Central Study Contacts

Aiping Zhou, doctor

CONTACT

86 13691161998; zhouap1825@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: UNKNOWN
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician

Model Details: 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

Study Record Dates

• First Submitted: January 16, 2022
• First Posted: February 1, 2022
• Study Start: April 1, 2022
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2025
• Last Updated: April 6, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)