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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04661150

Collaborator

(none)

Enrollment

Locations

Arms

49.6

Anticipated Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Gastroesophageal Junction Adenocarcinoma	Drug: Atezolizumab Drug: Trastuzumab Drug: Capecitabine Drug: Oxaliplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Mar 12, 2021

Anticipated Primary Completion Date :

Jan 15, 2023

Anticipated Study Completion Date :

Apr 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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. Other Names: Tecentriq Drug: 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. Other Names: Herceptin Drug: Capecitabine Capecitabine 1000 mg/m^2 will be administered twice orally on Days 1-14, repeated every 3 weeks. Drug: Oxaliplatin Oxaliplatin 130 mg/m^2 will be administered by IV on Day 1 of a 21-day cycle.
Active Comparator: 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.	Drug: 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. Other Names: Herceptin Drug: Capecitabine Capecitabine 1000 mg/m^2 will be administered twice orally on Days 1-14, repeated every 3 weeks. Drug: Oxaliplatin Oxaliplatin 130 mg/m^2 will be administered by IV on Day 1 of a 21-day cycle.

Arm

Intervention/Treatment

Experimental: 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.

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.

Other Names:

Tecentriq

Drug: 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.

Other Names:

Herceptin

Drug: Capecitabine

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

Drug: Oxaliplatin

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

Active Comparator: 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.

Drug: Trastuzumab

Other Names:

Herceptin

Drug: Capecitabine

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

Drug: Oxaliplatin

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	China	100142
2	West China Hospital, Sichuan University; Department of Breast	Chengdu	China	610041
3	Nanfang Hospital, Southern Medical University	Guangzhou	China	510515
4	Sir Run Run Shaw Hospital	Hangzhou	China	310016
5	Harbin Medical University Cancer Hospital	Harbin	China	150081
6	Fudan University Shanghai Cancer Center; Medical Oncology	Shanghai City	China	201315
7	Zhongshan Hospital Fudan University	Shanghai	China	200032
8	Liaoning Provincial Cancer Hospital	Shengyang	China	110042
9	First Hospital of China Medical University; Surgery	Shenyang City	China	110001
10	Tianjin Medical University Cancer Institute & Hospital	Tianjing	China	300060
11	Zhejiang Cancer Hospital	Zhejiang	China	310022