Testing Immunotherapy (Atezolizumab) With or Without Chemotherapy in Locoregional MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer

April 6, 2024 updated by: National Cancer Institute (NCI)

A Randomized Phase II Study of Perioperative Atezolizumab +/- Chemotherapy in Resectable MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer

This phase II trial compares atezolizumab in combination with chemotherapy (docetaxel, oxaliplatin, leucovorin calcium, fluorouracil, capecitabine) to atezolizumab alone for controlling the growth and/or spreading of the disease in patients with gastric or gastroesophageal junction (JEG) cancer that has not spread from where it first started (local) or only has spread to nearby lymph nodes or tissue (locoregional) and has high microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). The mismatch repair (MMR) system in the body corrects errors made during the copying of DNA and serves as a proofreading function. If this system isn't working correctly, mutations (changes) in DNA occur which can allow the cancer to grow or spread. This is called dMMR (deficient mismatch repair) . MSI-H describes cancer cells that have a high number of mutations within microsatellites. For example, microsatellite testing that shows mutations in 30% or more microsatellites is called microsatellite instability-high (MSI-H). Microsatellites are short, repeated sequences of DNA. There is evidence that MSI-H/ dMMR gastric or GEJ tumors respond well to immunotherapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill tumor cells. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Chemotherapy drugs such as leucovorin calcium and fluorouracil work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Using atezolizumab as immunotherapy with and following chemotherapy versus atezolizumab alone prior to and after surgery may shrink or stabilize the tumor in patients with MSI-H/dMMR localized gastric or GEJ cancer and may increase the length of time after treatment that cancer does not come back or get worse.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare three-year event-free survival (EFS) following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab alone in patients with resectable microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) gastric and gastroesophageal junction (GEJ) cancer.

SECONDARY OBJECTIVES:

I. To assess tumor regression grade (TRG) rates following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

II. To assess overall survival (OS) following the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

III. To assess the toxicity associated with the administration of perioperative atezolizumab and chemotherapy versus atezolizumab in patients with resectable MSI-H/dMMR gastric and gastroesophageal junction (GEJ) cancer.

IV. To correlate circulating tumor-derived deoxyribonucleic acid (ctDNA) clearance (defined as > 50% reduction or a reduction to undetectable levels) with TRG, EFS and OS.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

NEOADJUVANT THERAPY: Patients receive physician's choice of chemotherapy regimen consisting of 4 cycles of docetaxel intravenously (IV), oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV (FLOT) or 4 cycles of oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV (mFOLFOX) or 3 cycles of oxaliplatin IV and capecitabine orally (PO) (CAPOX) in addition to atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive FLOT, mFOLFOX, or CAPOX and atezolizumab IV as in Neoadjuvant Therapy and then receive atezolizumab IV alone.

ARM B:

NEOADJUVANT THERAPY: Patients receive 3 cycles of atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive 9 cycles of atezolizumab IV on study.

All patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may optionally undergo positron emission tomography (PET)/CT and/or collection of blood samples throughout the trial. Patients may also undergo echocardiography (ECHO) throughout the trial as clinically indicated.

Patients are followed up for 10 years from the date of randomization.

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
    • Illinois
      • Bloomington, Illinois, United States, 61704
        • Recruiting
        • Illinois CancerCare-Bloomington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Canton, Illinois, United States, 61520
        • Recruiting
        • Illinois CancerCare-Canton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Carthage, Illinois, United States, 62321
        • Recruiting
        • Illinois CancerCare-Carthage
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Dixon, Illinois, United States, 61021
        • Recruiting
        • Illinois CancerCare-Dixon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 815-285-7800
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Eureka, Illinois, United States, 61530
        • Recruiting
        • Illinois CancerCare-Eureka
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Galesburg, Illinois, United States, 61401
        • Recruiting
        • Illinois CancerCare-Galesburg
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Kewanee, Illinois, United States, 61443
        • Recruiting
        • Illinois CancerCare-Kewanee Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Macomb, Illinois, United States, 61455
        • Recruiting
        • Illinois CancerCare-Macomb
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Ottawa, Illinois, United States, 61350
        • Recruiting
        • Illinois CancerCare-Ottawa Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Pekin, Illinois, United States, 61554
        • Recruiting
        • Illinois CancerCare-Pekin
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois CancerCare-Peoria
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peru, Illinois, United States, 61354
        • Recruiting
        • Illinois CancerCare-Peru
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Princeton, Illinois, United States, 61356
        • Recruiting
        • Illinois CancerCare-Princeton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Shiloh, Illinois, United States, 62269
        • Recruiting
        • Memorial Hospital East
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Memorial Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Washington, Illinois, United States, 61571
        • Recruiting
        • Illinois CancerCare - Washington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
    • Indiana
      • Crown Point, Indiana, United States, 46307
        • Recruiting
        • Northwest Cancer Center - Main Campus
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
          • Site Public Contact
          • Phone Number: 219-310-2550
      • Dyer, Indiana, United States, 46311
        • Recruiting
        • Northwest Oncology LLC
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
          • Site Public Contact
          • Phone Number: 219-924-8178
      • Hobart, Indiana, United States, 46342
        • Recruiting
        • Northwest Cancer Center - Hobart
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
          • Site Public Contact
          • Phone Number: 219-947-1795
      • Hobart, Indiana, United States, 46342
        • Recruiting
        • Saint Mary Medical Center
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Indianapolis, Indiana, United States, 46312
        • Recruiting
        • Saint Catherine Hospital
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Munster, Indiana, United States, 46321
        • Recruiting
        • The Community Hospital
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
          • Site Public Contact
          • Phone Number: 219-836-3349
      • Munster, Indiana, United States, 46321
        • Recruiting
        • Women's Diagnostic Center - Munster
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
      • Valparaiso, Indiana, United States, 46383
        • Recruiting
        • Northwest Cancer Center - Valparaiso
        • Principal Investigator:
          • Suparna Mantha
        • Contact:
    • Iowa
      • Ames, Iowa, United States, 50010
        • Recruiting
        • Mary Greeley Medical Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Ames, Iowa, United States, 50010
        • Recruiting
        • McFarland Clinic - Ames
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
      • Ankeny, Iowa, United States, 50023
        • Recruiting
        • Mission Cancer and Blood - Ankeny
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
          • Site Public Contact
          • Phone Number: 515-282-2921
      • Boone, Iowa, United States, 50036
        • Recruiting
        • McFarland Clinic - Boone
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Medical Oncology and Hematology Associates-Des Moines
        • Principal Investigator:
          • Joshua Lukenbill
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • Mercy Medical Center - Des Moines
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Iowa Methodist Medical Center
        • Principal Investigator:
          • Joshua Lukenbill
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-6727
      • Fort Dodge, Iowa, United States, 50501
        • Recruiting
        • McFarland Clinic - Trinity Cancer Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Jefferson, Iowa, United States, 50129
        • Recruiting
        • McFarland Clinic - Jefferson
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Marshalltown, Iowa, United States, 50158
        • Recruiting
        • McFarland Clinic - Marshalltown
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Battle Creek, Michigan, United States, 49017
        • Recruiting
        • Bronson Battle Creek
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Brighton, Michigan, United States, 48114
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Canton, Michigan, United States, 48188
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Chelsea, Michigan, United States, 48118
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Cancer and Blood Disease Treatment Center
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Spectrum Health at Butterworth Campus
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • Bronson Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • West Michigan Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49009
        • Recruiting
        • Ascension Borgess Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Justin Shaya
      • Muskegon, Michigan, United States, 49444
        • Recruiting
        • Trinity Health Muskegon Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Norton Shores, Michigan, United States, 49444
        • Recruiting
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
        • Principal Investigator:
          • Kathleen J. Yost
        • Contact:
      • Reed City, Michigan, United States, 49677
        • Recruiting
        • Corewell Health Reed City Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Saint Joseph, Michigan, United States, 49085
        • Recruiting
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Traverse City, Michigan, United States, 49684
        • Recruiting
        • Munson Medical Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Wyoming, Michigan, United States, 49519
        • Recruiting
        • University of Michigan Health - West
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Justin Shaya
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Farmington, Missouri, United States, 63640
        • Recruiting
        • Parkland Health Center - Farmington
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Saint Louis, Missouri, United States, 63131
        • Recruiting
        • Missouri Baptist Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Saint Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Saint Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Contact:
        • Principal Investigator:
          • Patrick Grierson
      • Sainte Genevieve, Missouri, United States, 63670
        • Recruiting
        • Sainte Genevieve County Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sullivan, Missouri, United States, 63080
        • Recruiting
        • Missouri Baptist Sullivan Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
      • Sunset Hills, Missouri, United States, 63127
        • Recruiting
        • BJC Outpatient Center at Sunset Hills
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 314-996-5569
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 212-824-7309
          • Email: CCTO@mssm.edu
        • Principal Investigator:
          • Lakshmi Rajdev
      • New York, New York, United States, 10019
        • Recruiting
        • Mount Sinai West
        • Contact:
          • Site Public Contact
          • Phone Number: 212-824-7309
          • Email: CCTO@mssm.edu
        • Principal Investigator:
          • Lakshmi Rajdev
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Sagila George
    • Oregon
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19103
        • Recruiting
        • ECOG-ACRIN Cancer Research Group
        • Principal Investigator:
          • Lakshmi Rajdev
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Principal Investigator:
          • Jennifer L. Myers
        • Contact:
      • Richmond, Virginia, United States, 23235
        • Recruiting
        • VCU Massey Cancer Center at Stony Point
        • Principal Investigator:
          • Jennifer L. Myers
        • Contact:
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center
        • Principal Investigator:
          • Nataliya V. Uboha
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient must be >= 18 years of age

  • Patient must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma that is MSI-H/dMMR (microsatellite instability-high/mismatch repair deficient) as determined by one of three methods:

    • Deficient deoxyribonucleic acid (DNA) mismatch repair protein (MMR) expression status: MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR. dMMR may be determined either locally or by site-selected reference lab by Clinical Laboratory Improvement Act (CLIA)-certified assay

      • NOTE: Loss of MLH1 and PMS2 commonly occur together
    • Polymerase chain reaction (PCR) determined microsatellite instability
    • MSI-H tumor status determined by next-generation sequencing

  • Patient must have previously untreated localized gastric, or Siewert type II or III GEJ (gastroesophageal junction) adenocarcinoma. Tumors must be staged as T2 or greater primary lesion or be any T stage with the presence of positive locoregional lymph nodes- N+ (clinical nodes) without evidence of metastatic disease

    • Siewert type II tumors: tumors located between 1 cm proximal and 2 cm distal to the GEJ
    • Siewert type III tumors: tumors located between 2 and 5 cm distal to GEJ
  • Patient must be amenable to surgical resection with therapeutic intent
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 14 days prior to randomization)
  • Platelets >= 100,000/mcL (obtained =< 14 days prior to randomization)
  • Hemoglobin >= 9 g/dL (obtained =< 14 days prior to randomization)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =< ULN (for patients with total bilirubin > 1.5 x ULN) (obtained =< 14 days prior to randomization)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): x =< 3 institutional ULN (obtained =< 14 days prior to randomization)
  • Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) > 50 mL/min/1.73m^2 (obtained =< 14 days prior to randomization)
  • Albumin >= 2.5 g/dL (obtained =< 14 days prior to randomization)
  • International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time [PTT] is within therapeutic range of intended use of anticoagulants) (obtained =< 14 days prior to randomization)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) (obtained =< 14 days prior to randomization)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patient must have no contraindications to receive one of the chemotherapy regimens: FLOT or mFOLFOX / CAPOX
  • Patient must not have had prior potentially curative surgery for carcinoma of the stomach/GEJ
  • Patient must not receive any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
  • Patient must have recovered from clinically significant adverse events of their most recent therapy/intervention prior to randomization
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patient must have chest/abdomen/pelvis CT completed within 4 weeks prior to randomization
  • Patient may not have received prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CTLA4 monoclonal antibody)
  • Patient must not have received any live vaccines within 30 days prior to randomization and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist [registered trademark] are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)

  • Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain- Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis and hepatitis. Patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome are ineligible because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but otherwise are eligible.

    • Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
  • Patients must not be receiving systemic steroid therapy equivalent to > 10 mg prednisone per day or any other form of immunosuppressive therapy within 7 days prior to randomization. Topical corticosteroid or occasional inhaled corticosteroids are allowed
  • Patient must not have known interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity, and must not have a known history of prior pneumonitis requiring treatment with steroids, or any evidence of active, non-infectious pneumonitis
  • Patient must not have a known history of active TB (Bacillus Tuberculosis)
  • Patient must not have any hypersensitivity to atezolizumab or any of its excipients
  • Patient must not have received any prior chemotherapy, targeted small molecule therapy, or radiation therapy for their MSI-H/dMMR gastric and GEJ cancer
  • Patient must not have had an allogeneic bone marrow/stem, cell or solid organ transplant
  • Patient must not have a history or current evidence of any condition (e.g., known deficiency of the enzyme dihydropyrimidine dehydrogenase [DPD]), therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
  • Patient must not have any condition that would interfere with the cooperation with the requirements of this trial

  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used

    • All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy
    • A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse while on protocol treatment. Patients of childbearing potential must continue contraception measures for 5 months after the last dose of atezolizumab and for 9 months after the last dose of chemotherapy. Male patients with partners of childbearing potential must continue contraception measures for 6 months after the last dose of chemotherapy. Patients of childbearing potential must also not breastfeed while on treatment and for 5 months after the last dose of atezolizumab and for 3 months after the last dose of chemotherapy
  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • The investigator must declare the chemotherapy regimen their patient will receive (FLOT or mFOLFOX / CAPOX) prior to randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm B (atezolizumab)

NEOADJUVANT THERAPY: Patients receive atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive atezolizumab IV on study.

Patients also undergo CT or MRI throughout the trial. Patients may optionally undergo PET/CT and/or collection of blood samples throughout the trial. Patients may also undergo ECHO throughout the trial as clinically indicated.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Surgical Procedure
Undergo surgery
Other Names:
  • Operation
  • Surgery
  • Surgery Type
  • Surgical
  • Surgical Intervention
  • Surgical Interventions
  • Surgical Procedures
  • Type of Surgery
  • Surgery, NOS
Biological: Atezolizumab
Given IV
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
Procedure: Echocardiography
Undergo ECHO
Other Names:
  • EC
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Lymphadenectomy
Undergo lymphadenectomy
Other Names:
  • excision of the lymph node
  • Lymph Node Dissection
  • Lymph Node Excision
Experimental: Arm A (chemotherapy, atezolizumab)

NEOADJUVANT THERAPY: Patients receive physician's choice of chemotherapy regimen consisting of FLOT or mFOLFOX or CAPOX in addition to atezolizumab IV on study.

SURGERY: Patients undergo surgery with lymphadenectomy on study.

ADJUVANT THERAPY: Patients receive FLOT, mFOLFOX, or CAPOX and atezolizumab IV as in neoadjuvant therapy and then receive atezolizumab IV alone.

Patients also undergo CT or MRI throughout the trial. Patients may optionally undergo PET/CT and/or collection of blood samples throughout the trial. Patients may also undergo ECHO throughout the trial as clinically indicated.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Docetaxel
Given IV
Other Names:
  • Taxotere
  • Docecad
  • RP56976
  • Taxotere Injection Concentrate
  • RP 56976
Procedure: Surgical Procedure
Undergo surgery
Other Names:
  • Operation
  • Surgery
  • Surgery Type
  • Surgical
  • Surgical Intervention
  • Surgical Interventions
  • Surgical Procedures
  • Type of Surgery
  • Surgery, NOS
Biological: Atezolizumab
Given IV
Other Names:
  • Tecentriq
  • MPDL3280A
  • RO5541267
  • RG7446
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL328OA
Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluracil
  • Fluracil
  • 5 Fluorouracil
  • 5 Fluorouracilum
  • 5 FU
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fu
  • 5FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757
Drug: Oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • Ai Heng
  • Aiheng
  • Diaminocyclohexane Oxalatoplatinum
  • Eloxatine
  • JM-83
  • Oxalatoplatin
  • Oxalatoplatinum
  • RP 54780
  • RP-54780
  • SR-96669
Drug: Capecitabine
Given PO
Other Names:
  • Xeloda
  • Ro 09-1978/000
Drug: Leucovorin Calcium
Given IV
Other Names:
  • Wellcovorin
  • Adinepar
  • Calcifolin
  • Calcium (6S)-Folinate
  • Calcium Folinate
  • Calcium Leucovorin
  • Calfolex
  • Calinat
  • Cehafolin
  • Citofolin
  • Citrec
  • Citrovorum Factor
  • Cromatonbic Folinico
  • Dalisol
  • Disintox
  • Divical
  • Ecofol
  • Emovis
  • Factor, Citrovorum
  • Flynoken A
  • Folaren
  • Folaxin
  • FOLI-cell
  • Foliben
  • Folidan
  • Folidar
  • Folinac
  • Folinate Calcium
  • Folinic Acid Calcium Salt Pentahydrate
  • Folinoral
  • Folinvit
  • Foliplus
  • Folix
  • Imo
  • Lederfolat
  • Lederfolin
  • Leucosar
  • leucovorin
  • Rescufolin
  • Rescuvolin
  • Tonofolin
  • Folinic acid
Procedure: Echocardiography
Undergo ECHO
Other Names:
  • EC
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Lymphadenectomy
Undergo lymphadenectomy
Other Names:
  • excision of the lymph node
  • Lymph Node Dissection
  • Lymph Node Excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: From randomization to systemic progression of disease that precludes surgery or distant recurrence, or death due to any cause, assessed up to 3 years
EFS is defined as the time from randomization to an unfavorable event. Hence, occurrences such as local, resectable recurrences, patients' refusal for surgery of resectable tumor, or patients' undergoing definitive therapy such as salvage surgery would not be counted as events for EFS.
From randomization to systemic progression of disease that precludes surgery or distant recurrence, or death due to any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor regression grade (TRG)
Time Frame: Up to 10 years
Will be assessed in the primary tumor using Becker's grading criteria. Fisher's exact test will be used to compare the TRG across the arms.
Up to 10 years
Overall survival (OS)
Time Frame: From randomization to death from any cause, assessed up to 10 years
The stratified log rank test will be used to compare OS across the arms.
From randomization to death from any cause, assessed up to 10 years
Incidence of adverse events
Time Frame: Up to 10 years
All adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Formal comparison (hypothesis testing) of toxicity rates across the arms is not a primary goal of this trial and the sample size of 240 patients will provide sufficient power for detecting only relatively large differences in adverse events.
Up to 10 years
Circulating tumor-derived deoxyribonucleic acid (ctDNA)
Time Frame: Up to 10 years
The proportion of ctDNA clearance on each arm would be correlated with time-to-event (EFS and OS) and binary (TRG) data of the trial. For correlating ctDNA clearance rates and time-to-event data, cox-regression would be used to estimate the correlation magnitude. For correlating ctDNA and binary data, proportions of ctDNA clearances will be compared.
Up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Lakshmi Rajdev, ECOG-ACRIN Cancer Research Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2023

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

April 26, 2023

First Submitted That Met QC Criteria

April 26, 2023

First Posted (Actual)

May 1, 2023

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 6, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2023-03192 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180820 (U.S. NIH Grant/Contract)
  • EA2212 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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