Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
Conditions
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.
Interventions
DRUGAtezolizumab
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.
DRUGTrastuzumab
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.
DRUGCapecitabine
Capecitabine 1000 mg/m\^2 will be administered twice orally on Days 1-14, repeated every 3 weeks.
DRUGOxaliplatin
Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Regression (pCR) Rate | Completion of neoadjuvant systemic therapy (up to approximately 16 months) | 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
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | Randomization to the first documented disease recurrence, unequivocal tumor progression or death from any cause, whichever occurs first (up to approximately 52 months) | 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) | Surgery to first documented disease recurrence or death from any cause, whichever occurs first (up to approximately 52 months) | 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) | Randomiation to death from any cause (up to approximately 52 months) | Overall survival (OS), defined as the time from randomization to death from any cause in all patients. |
| Major Pathologic Response (MPR) | Randomization up to approximately 16 months | 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) | Randomiation to CR or PR during neoadjuvant systemic therapy (up to approximately 16 months) | 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 | Surgery | 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 | Baseline through the end of study (approximately 52 months) | — |
Countries
China
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Atezolizumab Plus Trastuzumab With XELOX (Capecitabine + Oxaliplatin) Participants received atezolizumab + trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, participants received 5 further cycles of this regimen. | 21 |
| Arm B: Trastuzumab With XELOX (Capecitabine + Oxaliplatin) Participants received trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, participants received 5 further cycles of this regimen. | 21 |
| Total | 42 |
Baseline characteristics
| Characteristic | Arm A: Atezolizumab Plus Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Arm B: Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Total |
|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 9.03 | 63.2 Years STANDARD_DEVIATION 6.28 | 61.5 Years STANDARD_DEVIATION 7.86 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 21 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 19 Participants | 20 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 21 | 0 / 21 |
| other Total, other adverse events | 6 / 21 | 5 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
Primary
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..
Time frame: Completion of neoadjuvant systemic therapy (up to approximately 16 months)
Population: Intention-to-treat (ITT) population, defined as all participants who were randomly assigned to a treatment, regardless of whether they had surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Atezolizumab Plus Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Pathological Complete Regression (pCR) Rate | 38.1 Percentage of Participants |
| Arm B: Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Pathological Complete Regression (pCR) Rate | 14.3 Percentage of Participants |
p-value: 0.07990% CI: [1.3, 44.7]Chi-squared
Secondary
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.
Time frame: Surgery to first documented disease recurrence or death from any cause, whichever occurs first (up to approximately 52 months)
Secondary
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.
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)
Secondary
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.
Time frame: Randomization up to approximately 16 months
Secondary
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.
Time frame: Randomiation to CR or PR during neoadjuvant systemic therapy (up to approximately 16 months)
Population: Intention-to-treat (ITT) population, defined as all participants who were randomly assigned to a treatment, regardless of whether they had surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Atezolizumab Plus Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Objective Response Rate (ORR) | 28.6 Percentage of participants |
| Arm B: Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | Objective Response Rate (ORR) | 33.3 Percentage of participants |
p-value: 0.73990% CI: [-27.9, 18.9]Chi-squared
Secondary
Overall Survival (OS)
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)
Secondary
Percentage of Participants With Adverse Events
Time frame: Baseline through the end of study (approximately 52 months)
Secondary
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.
Time frame: Surgery
Population: Intention-to-treat (ITT) population, defined as all participants who were randomly assigned to a treatment, regardless of whether they had surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: Atezolizumab Plus Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | R0 Resection Rate | 95.2 Percentage of particpants |
| Arm B: Trastuzumab With XELOX (Capecitabine + Oxaliplatin) | R0 Resection Rate | 90.5 Percentage of particpants |
p-value: >0.99990% CI: [-10.9, 21.4]Fisher Exact