A Study of Atezolizumab and Trastuzumab in Combination With Capecitabine and Oxaliplatin in Patients With HER2 Positive Locally Advanced Resectable Gastric Cancer of Adenocarcinoma of Gastroesophageal Junction

NCT ID: NCT04661150

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-12
• Study Completion Date: 2026-07-30

Brief Summary

This is a phase II, multicenter, randomized, open-label study designed to evaluate the efficacy and safety of perioperative trastuzumab+XELOX with / without atezolizumab in participants eligible for surgery with locally advanced HER2-positive gastric cancer or adenocarcinoma of GEJ.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Study Design

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

Study Groups

Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Participants will receive atezolizumab + trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, patrticipants will receive 5 further cycles of this regimen.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered as an 8 mg/kg IV loading dose and then 6 mg/kg IV on Day 1 of a 21-day cycle for 3 cycles before surgery, and administration will continue after surgery. The first administration of trastuzumab after surgery should also be given at the loading dose of 8 mg/kg.

Capecitabine

Intervention Type: DRUG

Capecitabine 1000 mg/m\^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 3 cycles prior to surgery and 5 cycles after surgery.

Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)

Participants will receive trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, participants will receive 5 further cycles of this regimen.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

Trastuzumab will be administered as an 8 mg/kg IV loading dose and then 6 mg/kg IV on Day 1 of a 21-day cycle for 3 cycles before surgery, and administration will continue after surgery. The first administration of trastuzumab after surgery should also be given at the loading dose of 8 mg/kg.

Capecitabine

Intervention Type: DRUG

Capecitabine 1000 mg/m\^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.

Oxaliplatin

Intervention Type: DRUG

Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle.

Interventions

Trastuzumab

Trastuzumab will be administered as an 8 mg/kg IV loading dose and then 6 mg/kg IV on Day 1 of a 21-day cycle for 3 cycles before surgery, and administration will continue after surgery. The first administration of trastuzumab after surgery should also be given at the loading dose of 8 mg/kg.

Intervention Type: DRUG

Capecitabine

Capecitabine 1000 mg/m\^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.

Intervention Type: DRUG

Oxaliplatin

Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle for 3 cycles prior to surgery and 5 cycles after surgery.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Herceptin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed gastric cancer or adenocarcinoma of GEJ
• HER2-positive status defined as either IHC score of 3+ or IHC 2+ with amplification proven by in situ hybridization (ISH) as assessed by local review based on pretreatment endoscopic biopsies.
• Clinical stage at presentation: cT3/T4a/T4b, or N+, M0 as determined by AJCC staging system, 8th edition
• Availability of pretreatment tumor specimen for biomarker analysis by central lab
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy >= 12 weeks
• Adequate hematologic and end-organ function
• For female patients of childbearing potential, agreement (by patient) to remain abstinent (refrain from heterosexual intercourse) or to use highly effective form(s) of contraception during the treatment period and to continue its use for at least i) 5 months after the last dose of atezolizumab, ii) 7 months after the last dose of trastuzumab, or iii) 6 months after the last dose of capecitabine or oxaliplatin, whichever is longer.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Exclusion Criteria

• Stage IV (metastatic) or unresectable gastric/GEJ cancer determined by investigators
• Prior systemic therapy for treatment of gastric cancer
• History of malignancy other than GC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Cardiopulmonary dysfunction
• Dyspnea at rest
• Active or history of autoimmune disease or immune deficiency with the following exceptions: (a) Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid-replacement hormone are eligible for the study. (b) Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. (c) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided allof following conditions are met: (i) Rash must cover < 10% of body surface area (ii) Disease is well controlled at baseline and requires only low-potency topical corticosteroids (iii) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Active tuberculosis
• Patients with active hepatitis B
• Patients with active hepatitis C

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

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Beijing Cancer Hospital

Beijing, , China

West China Hospital, Sichuan University

Chengdu, , China

Nanfang Hospital, Southern Medical University

Guangzhou, , China

Harbin Medical University Cancer Hospital

Harbin, , China

Zhongshan Hospital Fudan University

Shanghai, , China

Liaoning Provincial Cancer Hospital

Shengyang, , China

First Hospital of China Medical University

Shenyang, , China

Tianjin Medical University Cancer Institute & Hospital

Tianjing, , China

Countries

China

References

Peng Z, Zhang X, Liang H, Zheng Z, Wang Z, Liu H, Hu J, Sun Y, Zhang Y, Yan H, Tong L, Xu J, Ji J, Shen L. Atezolizumab and Trastuzumab Plus Chemotherapy for ERBB2-Positive Locally Advanced Resectable Gastric Cancer: A Randomized Clinical Trial. JAMA Oncol. 2025 Jun 1;11(6):619-624. doi: 10.1001/jamaoncol.2025.0522.

Reference Type: DERIVED

PMID: 40244574 (View on PubMed)

Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

Reference Type: DERIVED

PMID: 35623069 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ML42058

Identifier Type: -

Identifier Source: org_study_id