Atezolizumab + Chemotherapy for Stomach and Esophageal Cancer

Recruiting at 155 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immune checkpoint inhibitors, Live vaccines

Disqualifiers: Autoimmune disease, Cardiac disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 13

240 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot receive any other standard anti-cancer therapy or experimental agent concurrently with the study drugs, and you must not be on systemic steroid therapy equivalent to more than 10 mg of prednisone per day within 7 days prior to randomization.

What data supports the effectiveness of the drug combination Atezolizumab, Tecentriq, Oxaliplatin, Capecitabine, Docetaxel, Fluorouracil, and Leucovorin Calcium for stomach and esophageal cancer?

Research shows that combining immune checkpoint inhibitors like nivolumab with oxaliplatin-based chemotherapy can have a sustained antitumor effect in advanced gastric cancer. Additionally, combinations of fluoropyrimidines and platinum, such as capecitabine with oxaliplatin, are widely accepted as standard treatments for advanced gastric and gastroesophageal cancers. ^{1 2 3 4 5}

Is the combination of Atezolizumab and chemotherapy safe for treating stomach and esophageal cancer?

Research on similar chemotherapy combinations, like capecitabine with oxaliplatin or docetaxel, shows they are generally safe but can have severe side effects. These treatments have been studied for stomach and esophageal cancers, indicating they are used with caution due to potential adverse effects. ^{1 6 7 8 9}

What makes the drug Atezolizumab + Chemotherapy unique for stomach and esophageal cancer?

This treatment combines atezolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with chemotherapy drugs like oxaliplatin and capecitabine. This combination aims to enhance the effectiveness of chemotherapy by also engaging the body's immune response, which is a novel approach compared to traditional chemotherapy alone. ^{4 5 10 11 12}

Research Team

Lakshmi Rajdev

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Adults with untreated localized gastric or gastroesophageal junction adenocarcinoma that is MSI-H/dMMR, meaning their cancer cells have a high number of mutations. They must be fit for surgery, have not had prior curative surgery for this cancer type, and should not have received immune checkpoint inhibitors before. People with severe autoimmune diseases or those who recently received live vaccines are excluded.

Inclusion Criteria

I am eligible for surgery aimed at treating my condition.

My doctor has decided on my chemotherapy plan before any treatment assignment.

Patient must not have any condition that would interfere with the cooperation with the requirements of this trial

Exclusion Criteria

I do not have an active autoimmune disease or a history that might need treatment.

I have never been treated with immune checkpoint inhibitors.

I do not have lung conditions that could affect treatment side effects.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Therapy

Patients receive chemotherapy regimen (FLOT, mFOLFOX, or CAPOX) with atezolizumab or atezolizumab alone

9-12 weeks

3-4 cycles of treatment

Surgery

Patients undergo surgery with lymphadenectomy

1 week

1 surgical visit

Adjuvant Therapy

Patients receive chemotherapy regimen (FLOT, mFOLFOX, or CAPOX) with atezolizumab or atezolizumab alone

9-12 weeks

9 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• Atezolizumab
• Oxaliplatin, Capecitabine, Docetaxel, Fluorouracil, Leucovorin Calcium

Trial Overview The trial compares the effectiveness of atezolizumab (an immunotherapy drug) combined with chemotherapy to atezolizumab alone in controlling tumor growth in patients with certain types of stomach cancers. The study will assess if these treatments can shrink tumors before and after surgery without the disease worsening.

Participant Groups

Group I: Arm B (atezolizumab) Experimental Treatment 8 Interventions

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.

Group II: Arm A (chemotherapy, atezolizumab) Experimental Treatment 13 Interventions

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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a meta-analysis of 1231 patients, pembrolizumab and paclitaxel showed no significant difference in effectiveness for treating advanced gastroesophageal cancer, with similar objective response rates.

Both treatments can be considered viable options for patients, as they provide comparable time to response and similar rates of partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. Swed, S., Shaheen, N., Hafez, W., et al.[2022]

The combination of nivolumab (an anti-PD-1 antibody) with irinotecan and a fluoropyrimidine showed a disease control rate of 73.3% in 15 patients with advanced unresectable gastroesophageal cancers, indicating potential efficacy in this challenging patient population.

The treatment was generally feasible, with a median progression-free survival of 7 months and overall survival of 13.3 months, although 33% of patients experienced dose delays or adjustments primarily due to fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. Rogers, JE., Xiao, L., Trail, A., et al.[2023]

In a phase 2 trial involving 155 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, bemarituzumab combined with mFOLFOX6 showed a median progression-free survival of 9.5 months compared to 7.4 months for the placebo group, indicating potential efficacy despite not reaching statistical significance.

The treatment was associated with a higher incidence of corneal disorders and treatment-related deaths, highlighting the need for careful monitoring of safety, particularly regarding ocular side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Wainberg, ZA., Enzinger, PC., Kang, YK., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

A randomized phase II trial comparing capecitabine with oxaliplatin or docetaxel as first-line treatment in advanced gastric and gastroesophageal adenocarcinomas. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus paclitaxel for previously treated, advanced gastro-esophageal junction cancer: A systematic review and meta-analysis of randomized clinical trials. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab in Combination with Irinotecan and 5-Fluorouracil (FOLFIRI) for Refractory Advanced Gastroesophageal Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: results of a randomised Phase 2 study. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer. [2019]

7. Greece pubmed.ncbi.nlm.nih.gov

Docetaxel and S-1 as a first-line treatment in patients with advanced or recurrent gastric cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

A Prospective Phase I/II Study of Docetaxel, Cisplatin and Continuous Capecitabine in Advanced Oesophago-Gastric Cancer (NWCOG-3). [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

A PERFECT Biomarker-focused Study of Neoadjuvant IO for Esophagogastric Cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Evolving therapies in advanced oesophago-gastric cancers and the increasing role of immunotherapy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. [2023]