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

Summary

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.

Conditions

• Clinical Stage I Gastric Cancer AJCC v8
• Clinical Stage I Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage II Gastric Cancer AJCC v8
• Clinical Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage III Gastric Cancer AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IVA Gastric Cancer AJCC v8
• Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Interventions

BIOLOGICAL

Atezolizumab

Given IV

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

DRUG

Capecitabine

Given PO

PROCEDURE

Computed Tomography

Undergo CT or PET/CT

DRUG

Docetaxel

Given IV

PROCEDURE

Echocardiography Test

Undergo ECHO

DRUG

Fluorouracil

Given IV

DRUG

Leucovorin Calcium

Given IV

PROCEDURE

Lymphadenectomy

Undergo lymphadenectomy

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Oxaliplatin

Given IV

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

PROCEDURE

Surgical Procedure

Undergo surgery

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Lakshmi Rajdev · ECOG-ACRIN Cancer Research Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-06

Primary Completion

2027-10-31

Completion

2027-10-31

FDA Drug

Yes

Countries

• United States

Study Locations