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

NCT ID: NCT05218148

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2025-12-01

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

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 Type: EXPERIMENTAL

sintilimab

Intervention Type: 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.

Trastuzumab

Intervention Type: 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.

S-1 plus oxaliplatin

Intervention Type: 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 B

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 Type: ACTIVE_COMPARATOR

S-1 plus oxaliplatin

Intervention Type: 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.

Interventions

sintilimab

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

Intervention Type: DRUG

Trastuzumab

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

Intervention Type: DRUG

S-1 plus oxaliplatin

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aiping Zhou

UNKNOWN

Sponsor Role: lead

Responsible Party

Aiping Zhou

Chief physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Cancer Hospital & Institute, Chinese Academy of Medical Sciences

Beijing, , China

Countries

China

Central Contacts

Aiping Zhou, doctor

Role: CONTACT

zhouap1825@126.com

86 13691161998

Other Identifiers

NCC-008261

Identifier Type: -

Identifier Source: org_study_id