Immunotherapy + Chemoradiation for Gastric Cancer

Overseen By Mariela Blum

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of treatments, including immunotherapy (using drugs like Ipilimumab and Nivolumab), chemotherapy (with drugs such as Fluorouracil and Oxaliplatin), and radiation (specifically Intensity-Modulated Radiation Therapy), to assess their effectiveness against surgically removable gastric cancer. The goal is to determine if these treatments together can enhance the immune system's ability to target and destroy cancer cells while minimizing harm to healthy tissues. Individuals who have not yet received treatment for their localized gastric cancer and are confirmed as surgical candidates may be suitable for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment.

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

Research has shown that the treatments tested in this trial, including nivolumab, ipilimumab, fluorouracil, oxaliplatin, and intensity-modulated radiation therapy (IMRT), have different safety profiles based on past studies.

Nivolumab is generally safe with chemotherapy, but serious side effects like fever and diarrhea occurred in 4% or more of patients. Ipilimumab, when combined with nivolumab, can be effective but may cause immune-related side effects. One study found severe side effects in 22% of patients using this combination.

Fluorouracil, a chemotherapy drug commonly used for many cancers, generally has manageable side effects. Oxaliplatin, another chemotherapy drug, has been shown to increase survival but can cause nerve-related issues, such as numbness.

IMRT, a type of radiation therapy, targets tumors more precisely, potentially reducing harm to nearby healthy tissue. It is preferred over older methods for its safety and control rates, although there are some concerns about doses to the spinal cord and bowel.

Overall, while each treatment has possible side effects, they are generally well-tolerated when managed correctly. Potential risks should always be discussed with healthcare providers when considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for gastric cancer because it integrates immunotherapy with traditional chemoradiation in a novel way. The inclusion of nivolumab and ipilimumab, both immune checkpoint inhibitors, aims to boost the body's immune response against cancer cells, potentially offering a more targeted attack than standard chemotherapy alone. Additionally, the use of Intensity-Modulated Radiation Therapy (IMRT) allows for highly precise radiation delivery, which could minimize damage to surrounding healthy tissues. This multi-faceted approach might enhance treatment effectiveness and reduce side effects, promising a new avenue for improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for gastric cancer?

In this trial, participants will receive a combination of treatments, including nivolumab and ipilimumab. Studies have shown that this combination can effectively treat stomach cancer, significantly reducing tumors in more than half of the patients. Nivolumab, when combined with chemotherapy, has also been proven to extend survival. Participants will also receive oxaliplatin and fluorouracil, which can further inhibit the growth and spread of cancer cells. Intensity-modulated radiation therapy (IMRT) precisely targets tumors, helping to protect healthy tissue. Together, these treatments attack cancer cells from different angles, increasing the chances of controlling the disease. ^{2 6 7 8 9}

Who Is on the Research Team?

Mariela Blum

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with resectable gastric or gastroesophageal junction adenocarcinoma, without prior systemic treatment for advanced disease. Participants must have adequate organ function and performance status, not be pregnant or breastfeeding, and agree to contraception if applicable. Exclusions include previous immunotherapy, certain allergies, active autoimmune diseases requiring steroids, other cancers within 3 years (with exceptions), HIV/AIDS positive status, and serious uncontrolled medical disorders.

Inclusion Criteria

Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.

My kidney function is within the required range for the study.

Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of treatment initiation).

Exclusion Criteria

I haven't taken high-dose steroids or immunosuppressants in the last 14 days.

White blood cell (WBC) < 2000/uL.

I haven't had any cancer except for certain skin, bladder, prostate, cervix, or breast cancers in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Chemotherapy

Patients receive oxaliplatin and fluorouracil intravenously. Treatment repeats every 14 days for up to 4 courses.

8 weeks

4 visits (in-person)

Immunotherapy and Chemoradiation

Patients receive nivolumab and ipilimumab, followed by fluorouracil and intensity-modulated radiation therapy (IMRT).

10 weeks

6 visits (in-person)

Surgical Resection

Patients undergo surgical resection 5-7 weeks after completing radiation therapy.

1 week

Adjuvant Nivolumab

Patients with residual disease may receive nivolumab post-surgery. Treatment repeats every 2 weeks for 8 courses, then every 4 weeks for up to 2 courses.

24 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up at 30 and 84 days, every 12 weeks for 2 years, then every 6-12 months for up to 3 years.

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Fluorouracil
• Intensity-Modulated Radiation Therapy
• Ipilimumab
• Nivolumab
• Oxaliplatin
• Therapeutic Conventional Surgery

Trial Overview The study tests the combination of nivolumab and ipilimumab (immunotherapies) with chemotherapy drugs oxaliplatin and fluorouracil plus intensity-modulated radiation therapy in treating resectable gastric cancer. The goal is to see how well this combo works by helping the immune system attack cancer while minimizing damage to healthy tissue.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, immunotherapy, IMRT) Experimental Treatment 6 Interventions

INDUCTION CHEMOTHERAPY: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV over 48 hours on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment with nivolumab repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Beginning course 4, patients also receive fluorouracil IV continuously for 5 days per week and undergo 25 fractions of IMRT for 5 weeks. Patients undergo surgical resection 5-7 weeks after completing radiation therapy. Within 8-12 weeks post-surgery, patients with residual disease may receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 courses (16 weeks) then every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Capecitabine, an oral prodrug of 5-fluorouracil, has been shown to be an effective and convenient alternative to infusional 5-FU in the treatment of esophageal, stomach, and pancreatic cancers when combined with irradiation.

Research is ongoing into the benefits of adding a COX-2 inhibitor to treatment regimens for upper gastrointestinal cancers, as these cancers often show high levels of COX-2 expression, which may enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COX-2 inhibitors as radiation sensitizers for upper GI tract cancers: esophagus, stomach, and pancreas. Rich, TA., Shepard, R.[2015]

S-1, an oral chemotherapy drug combining tegafur with modulators, has shown advantages over standard 5-FU-based treatments for gastric cancer in large Phase III studies, making it a recommended option in treatment guidelines.

S-1, either alone or in combination with cisplatin, is non-inferior to traditional 5-FU regimens while offering greater convenience and reduced toxicity, highlighting its potential for higher efficacy in treating gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-1 for the treatment of gastrointestinal cancer. Satoh, T., Sakata, Y.[2022]

In a phase 2 trial involving 63 anal cancer patients, dose-painted intensity modulated radiation therapy (DP-IMRT) did not significantly reduce the overall rate of grade 2+ gastrointestinal and genitourinary adverse events compared to conventional treatment, but it did show a notable reduction in grade 3+ gastrointestinal (21% vs. 36%) and dermatologic (23% vs. 49%) toxicities.

DP-IMRT was found to be feasible, but a high rate of pretreatment planning revisions (81%) highlights the need for careful real-time quality assurance in radiation therapy to ensure patient safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Kachnic, LA., Winter, K., Myerson, RJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4323368/

5-Fluorouracil Chemotherapy of Gastric Cancer Generates ... Background: 5-Fluorouracil (5Fu) chemotherapy is the first treatment of choice for advanced gastric cancer (GC), but its effectiveness is limited by drug ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3544046/

Effectiveness of 5-flurouracil-based neoadjuvant ... AIM: To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006291X21000280

5-Fluorouracil enhances the chemosensitivity of gastric ... We found the combination of 5-FU and TRAIL had a greater inhibitory effect on the proliferation of gastric cancer cells than 5-FU or TRAIL alone both in vivo ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.396

Perioperative chemotherapy with either S-1 or 5- ... Perioperative LOTS shows reasonable therapeutic efficacy and survival as compared with FLOT in patients with locally advanced gastric/GEJ cancer.

5. cancerindex.org cancerindex.org/Fluorouracil

Fluorouracil Overall response rate was 22.2% and disease control rate of the 11 patients was 36.4%. Median relative dose intensity of 5-FU was 100% (range=85 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10420378/

S-1 and 5-Fluorouracil-related adverse events in patients with ... The adverse events following S-1 and 5-FU treatment in patients with advanced gastric cancer were analyzed in this study. The results suggested ...

7. cancerresearchuk.org cancerresearchuk.org/about-cancer/treatment/drugs/fluorouracil

Fluorouracil (5FU) | Cancer information Fluorouracil (5FU) is a chemotherapy drug. It is a treatment for many different types of cancer. Find out how you have it, side effects and other important ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.4037

Pembrolizumab plus 5-fluorouracil (5-FU) and cisplatin for ... Conclusions: These data suggest the combination of pembro, cisplatin, and 5-FU has a manageable safety profile as first-line therapy in patients ...

9. cancer.org cancer.org/cancer/types/stomach-cancer/treating/chemotherapy.html

Stomach (Gastric) Cancer & Chemotherapy Drugs Many different chemo drugs can be used to treat stomach cancer, including: 5-FU (fluorouracil), often given along with leucovorin (folinic acid) ...