Back to resultsA 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
Primary Purpose
Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Atezolizumab
Trastuzumab
Capecitabine
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Gastric Cancer
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
Sites / Locations
- Beijing Cancer Hospital
- West China Hospital, Sichuan University; Department of Breast
- Nanfang Hospital, Southern Medical University
- Harbin Medical University Cancer Hospital
- Fudan University Shanghai Cancer Center; Medical Oncology
- Zhongshan Hospital Fudan University
- Liaoning Provincial Cancer Hospital
- First Hospital of China Medical University; Surgery
- Tianjin Medical University Cancer Institute & Hospital
- Zhejiang Cancer Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin)
Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Pathological Complete Regression (pCR) Rate
pCR is defined as no evidence of vital residual tumor cells on hematoxylin and eosin evaluation of the complete resected gastric/GEJ specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST), which will be reviewed by local pathologist..
Secondary Outcome Measures
Event-free survival (EFS)
Event-free survival (EFS), defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first.
Disease-Free Survival (DFS)
Disease-free survival (DFS), defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first.
Overall survival (OS)
Overall survival (OS), defined as the time from randomization to death from any cause in all patients.
Major Pathologic Response (MPR)
Major pathologic response (MPR), defined as < 10% residual tumor per tumor bed based on evaluation of the resected primary esophagogastric specimen by a local pathologist.
Objective Response Rate (ORR)
Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) or partial response (PR) during NAST, as determined by the investigator according to RECIST v1.1.
R0 Resection Rate
R0 resection rate, defined as the proportion of patients with a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed and/or sampled regional lymph nodes based on evaluation by the local pathologist.
Percentage of Participants With Adverse Events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04661150
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 12, 2021 (Actual)
Primary Completion Date
May 8, 2023 (Actual)
Study Completion Date
August 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
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
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
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
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine 1000 mg/m^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin 130 mg/m^2 will be administered by IV on Day 1 of a 21-day cycle.
Primary Outcome Measure Information:
Title
Pathological Complete Regression (pCR) Rate
Description
pCR is defined as no evidence of vital residual tumor cells on hematoxylin and eosin evaluation of the complete resected gastric/GEJ specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST), which will be reviewed by local pathologist..
Time Frame
Completion of neoadjuvant systemic therapy (up to approximately 16 months)
Secondary Outcome Measure Information:
Title
Event-free survival (EFS)
Description
Event-free survival (EFS), defined as the time from randomization to the first documented disease recurrence, unequivocal tumor progression determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first.
Time Frame
Randomization to the first documented disease recurrence, unequivocal tumor progression or death from any cause, whichever occurs first (up to approximately 52 months)
Title
Disease-Free Survival (DFS)
Description
Disease-free survival (DFS), defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first.
Time Frame
Surgery to first documented disease recurrence or death from any cause, whichever occurs first (up to approximately 52 months)
Title
Overall survival (OS)
Description
Overall survival (OS), defined as the time from randomization to death from any cause in all patients.
Time Frame
Randomiation to death from any cause (up to approximately 52 months)
Title
Major Pathologic Response (MPR)
Description
Major pathologic response (MPR), defined as < 10% residual tumor per tumor bed based on evaluation of the resected primary esophagogastric specimen by a local pathologist.
Time Frame
Randomization up to approximately 16 months
Title
Objective Response Rate (ORR)
Description
Objective response rate (ORR), defined as the proportion of patients with a complete response (CR) or partial response (PR) during NAST, as determined by the investigator according to RECIST v1.1.
Time Frame
Randomiation to CR or PR during neoadjuvant systemic therapy (up to approximately 16 months)
Title
R0 Resection Rate
Description
R0 resection rate, defined as the proportion of patients with a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed and/or sampled regional lymph nodes based on evaluation by the local pathologist.
Time Frame
Surgery
Title
Percentage of Participants With Adverse Events
Time Frame
Baseline through the end of study (approximately 52 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
ZIP/Postal Code
100142
Country
China
Facility Name
West China Hospital, Sichuan University; Department of Breast
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Nanfang Hospital, Southern Medical University
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
Harbin Medical University Cancer Hospital
City
Harbin
ZIP/Postal Code
150081
Country
China
Facility Name
Fudan University Shanghai Cancer Center; Medical Oncology
City
Shanghai City
ZIP/Postal Code
201315
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Liaoning Provincial Cancer Hospital
City
Shengyang
ZIP/Postal Code
110042
Country
China
Facility Name
First Hospital of China Medical University; Surgery
City
Shenyang City
ZIP/Postal Code
110001
Country
China
Facility Name
Tianjin Medical University Cancer Institute & Hospital
City
Tianjing
ZIP/Postal Code
300060
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Zhejiang
ZIP/Postal Code
310022
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Citations:
PubMed Identifier
35623069
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.
Results Reference
derived
Learn more about this trial
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
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