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

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — BIOLOGICAL
  Given IV
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Capecitabine — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo CT or PET/CT
• Docetaxel — DRUG
  Given IV
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Fluorouracil — DRUG
  Given IV
• Leucovorin Calcium — DRUG
  Given IV
• Lymphadenectomy — PROCEDURE
  Undergo lymphadenectomy
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Oxaliplatin — DRUG
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET/CT
• Surgical Procedure — PROCEDURE
  Undergo surgery

Study Details

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.

Key Dates

Start date

Dec 6, 2023

Status verified

May 2026

Primary completion

Oct 31, 2027

Completion

Oct 31, 2027

Study Design

Enrollment

240 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• 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.
• 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.

Primary Outcome Measure

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 ]

Locations (133)

Find similar trials in Dublin, CA

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