Atezolizumab + Chemotherapy for Stomach and Esophageal Cancer

Not currently recruiting at 162 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a combination of atezolizumab (an immunotherapy drug) and chemotherapy can control stomach or esophageal cancer that hasn't spread far from its origin. Atezolizumab helps the immune system attack cancer cells, while chemotherapy drugs stop cancer cells from growing and spreading. The trial compares the effects of using both treatments together versus using atezolizumab alone. People newly diagnosed with localized stomach or gastroesophageal cancer and specific genetic markers (MSI-H/dMMR) might be a good fit for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that atezolizumab, when combined with chemotherapy, is generally safe for patients with stomach or gastroesophageal junction cancer. Studies have found that this combination can significantly shrink tumors, with many patients experiencing a major reduction in their cancer. Some side effects occur, but they are usually manageable.

For patients receiving atezolizumab alone, the treatment is also considered safe. Common side effects include fatigue and skin reactions, but these are often mild. Both treatment options have shown promising results in controlling cancer spread and growth, with safety profiles suitable for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because atezolizumab offers a novel approach by harnessing the immune system to target and attack cancer cells, unlike traditional chemotherapy that directly targets rapidly dividing cells. Atezolizumab is a type of immunotherapy known as a PD-L1 inhibitor, which can potentially enhance the body's immune response against stomach and esophageal cancer. Additionally, the combination of atezolizumab with chemotherapy could improve outcomes by leveraging both immune and chemical strategies, potentially leading to more effective and durable responses compared to standard chemotherapy alone. This dual approach might offer patients new hope, especially for those who have limited options with existing treatments.

What evidence suggests that this trial's treatments could be effective for stomach and esophageal cancer?

Research has shown that atezolizumab, one of the treatments in this trial, can effectively treat stomach and esophageal cancer, particularly in patients with certain genetic features (MSI-H and dMMR). In this trial, some participants will receive atezolizumab combined with chemotherapy. Previous studies have demonstrated that this combination can lead to better outcomes for patients with advanced stomach or gastroesophageal junction cancer. Specifically, patients receiving this combination have experienced better control over cancer growth and spread. Atezolizumab helps the immune system attack cancer cells, while chemotherapy stops them from growing and dividing. Together, they may shrink tumors or keep them stable, delaying cancer progression. ^{2 4 6 7 8}

Who Is on the Research Team?

Lakshmi Rajdev

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

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Atezolizumab and Trastuzumab Plus Chemotherapy for ... This randomized clinical trial compares the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006909/

Atezolizumab and Trastuzumab Plus Chemotherapy for ... This randomized clinical trial compares the efficacy and safety of atezolizumab plus trastuzumab plus capecitabine and oxaliplatin chemotherapy ...

3. nature.com nature.com/articles/s41591-023-02758-x

Neoadjuvant atezolizumab plus chemotherapy in gastric ... In patients with advanced or metastatic G/GEJ cancer, randomized trials have shown improved clinical outcomes after anti-PD-L1 with chemotherapy ...

4. targetedonc.com targetedonc.com/view/neoadjuvant-atezolizumab-and-chemo-show-potential-in-gastric-gej-cancer

Neoadjuvant Atezolizumab and Chemo Show Potential in ... Using neoadjuvant atezolizumab followed by atezolizumab plus chemotherapy before surgery for gastric or gastroesophageal junction tumors appeared to be ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.312

A multicenter, randomized, open-label phase II study. The addition of atezolizumab to trastuzumab + XELOX therapy was effective in patients with HER2+ locally advanced resectable GC or adenocarcinoma of the GEJ.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10878980/

Neoadjuvant atezolizumab plus chemotherapy in gastric and ... In patients with advanced or metastatic G/GEJ cancer, randomized trials have shown improved clinical outcomes after anti-PD-L1 with chemotherapy compared to ...

7. esmo.org esmo.org/oncology-news/neoadjuvant-atezolizumab-plus-chemotherapy-is-safe-and-has-promising-activity-in-patients-with-gastric-and-gastro-oesophageal-junction-adenocarcinoma

Neoadjuvant Atezolizumab Plus Chemotherapy Is Safe ... A combination of neoadjuvant atezolizumab plus chemotherapy led to a major pathologic response (MPR) in 70% and a pathologic complete response (pCR) in 45% of ...

8. ecog-acrin.org ecog-acrin.org/clinical-trials/ea2212-stomach-cancer/

EA2212 - Clinical Trial for Stomach Cancer Study compares atezolizumab in combination with chemotherapy to atezolizumab alone for controlling the growth or spread of disease in patients with gastric ...