Clinical trial NCT04661150: 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
Official title: A Phase II, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) and Trastuzumab in Combination With Capecitabine and Oxaliplatin (Xelox) in Patients With HER2 Positive Locally Advanced Resectable Gastric Cancer of Adenocarcinoma of Gastroesophageal Junction (GEJ)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-12-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Pathological Complete Regression (pCR) Rate
timeFrame: Completion of neoadjuvant systemic therapy (up to approximately 16 months)
Secondary outcomes:
measure: Event-free Survival (EFS)
timeFrame: Randomization to the first documented disease recurrence, unequivocal tumor progression or death from any cause, whichever occurs first (up to approximately 52 months)
measure: Disease-Free Survival (DFS)
timeFrame: Surgery to first documented disease recurrence or death from any cause, whichever occurs first (up to approximately 52 months)
measure: Overall Survival (OS)
timeFrame: Randomiation to death from any cause (up to approximately 52 months)
measure: Major Pathologic Response (MPR)
timeFrame: Randomization up to approximately 16 months
measure: Objective Response Rate (ORR)
timeFrame: Randomiation to CR or PR during neoadjuvant systemic therapy (up to approximately 16 months)
measure: R0 Resection Rate
timeFrame: Surgery
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline through the end of study (approximately 52 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shengyang
country: China
facility: Liaoning Provincial Cancer Hospital
city: Shenyang City
country: China
facility: First Hospital of China Medical University
city: Tianjing
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.