Nivolumab + Radiation for Gastroesophageal Cancer

Not currently recruiting at 5 trial locations

Overseen By Carina Puello, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: FOLFOX, Nivolumab

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: HER2 positive, Active TB, Autoimmune, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug nivolumab (Opdivo), used alone or with radiation, can treat certain types of stomach and esophagus cancer that have not worsened with initial treatments. Participants will receive either nivolumab alone or in combination with radiation therapy. The researchers aim to determine which approach better controls the cancer. This trial may suit individuals with advanced gastroesophageal cancer who have already responded to initial treatment with FOLFOX and nivolumab. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you must stop these at least 7 days before starting the trial treatment.

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

Research shows that nivolumab is usually well-tolerated, whether used alone or with other treatments. Studies have demonstrated that nivolumab helps patients with advanced stomach and gastroesophageal cancers live longer compared to chemotherapy alone. A small number of patients, about 4% or more, reported serious side effects like fever, diarrhea, and low red blood cell count (anemia).

When combined with radiation, nivolumab has also provided benefits, though similar side effects can occur. These include increased liver enzymes, indicating liver stress, and adrenal insufficiency, where the body doesn’t produce enough hormones.

Since the FDA has already approved nivolumab for other uses, its safety profile is well-known. This means its side effects are understood and monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Nivolumab for gastroesophageal cancer because it works differently from traditional chemotherapy options like FOLFOX. Nivolumab is an immunotherapy drug that boosts the body's immune system to target and destroy cancer cells, offering a new way to treat this type of cancer. Additionally, when combined with radiation therapy, as in some experimental approaches, it might enhance the treatment's effectiveness by making cancer cells more susceptible to the immune response. This novel combination could potentially lead to better outcomes and fewer side effects compared to conventional treatments.

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

Research has shown that nivolumab, whether used alone or with chemotherapy, can help patients with advanced gastroesophageal cancer live longer. In this trial, participants will initially receive standard dose FOLFOX plus nivolumab. A study found that combining nivolumab with chemotherapy improved both overall survival and the time during which the cancer does not worsen. Participants who respond to this initial treatment will be randomized into two cohorts. In Cohort 1, participants will receive nivolumab alone. In Cohort 2, participants will receive nivolumab plus radiation therapy. Early signs suggest that adding radiation therapy to nivolumab could enhance the treatment's effectiveness, although more data is still being collected. This combination aims to leverage the benefits of immunotherapy along with the focused effects of radiation. ^{1 2 5 6 7}

Who Is on the Research Team?

Manish Shah, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Adults over 18 with advanced gastroesophageal adenocarcinoma that can't be surgically removed or has spread, who haven't progressed after initial FOLFOX and Nivolumab therapy. Participants need normal organ function, not pregnant, willing to use birth control, and able to provide a recent tumor tissue sample. Excludes those with immune deficiencies, active infections or other cancers within the last 3 years (with some exceptions), autoimmune diseases requiring treatment in the past 2 years, known HIV/Hepatitis B/C, or prior anti-PD-1/L1/L2 therapies.

Inclusion Criteria

Absolute neutrophil count ≥ 1,500/mL

I am older than 18 years.

I have advanced cancer that started in my stomach or esophagus and it can't be removed by surgery.

Exclusion Criteria

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

My cancer is HER2 positive adenocarcinoma.

I was treated for cancer other than prostate or skin cancer less than 3 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive FOLFOX plus nivolumab for 2 months. If stable disease is observed, treatment continues for an additional month.

3 months

Every 2 weeks

Randomized Treatment

Participants are randomized to receive either nivolumab alone or nivolumab plus radiation therapy.

1 month

Every 2 weeks for two doses, then every 4 weeks

Maintenance Therapy

Participants who remain on study receive nivolumab 480 mg every 4 weeks.

20 months

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab

Trial Overview This phase II trial is testing whether adding radiation therapy to nivolumab offers any benefit compared to nivolumab alone for patients whose cancer hasn't worsened following initial treatment with FOLFOX chemotherapy combined with nivolumab.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions)

Group II: Cohort 1 Experimental Treatment 1 Intervention

Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks)

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

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. opdivohcp.com opdivohcp.com/efficacy/gastro

Efficacy Data for Gastroesophageal Cancers - Opdivo The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01601

3-Year Follow-Up of the Phase III CheckMate 649 Trial At 12.1-month minimum follow-up, nivolumab plus chemotherapy demonstrated improvement in all efficacy measures, including superior overall ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11583461/

Efficacy and safety of Nivolumab in advanced gastric and ... Nivolumab, both alone and in combination with chemotherapy, improves OS and PFS in patients with advanced gastric and gastroesophageal junction cancer.

4. opdivo.com opdivo.com/gastroesophageal-cancer/clinical-trial-results/advanced-gastric-gej-esophageal-immunotherapy-chemo

Clinical trial results for advanced gastroesophageal cancer An FDA-approved combination of immunotherapy and chemotherapy that helped people live longer compared to chemotherapy alone.

5. esmogastro.org esmogastro.org/article/S2949-8198(24)00033-5/fulltext

Safety and efficacy of first-line nivolumab plus chemotherapy ... Nivolumab + chemotherapy has comparable efficacy and safety in real-world practice. An increasing DpR correlated with a numerically longer median OS.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2949819824000335

Safety and efficacy of first-line nivolumab plus ... At a median follow-up of 14.0 months, the median progression-free survival (PFS) and overall survival (OS) were 7.9 and 21.7 months, respectively. In patients ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2111380

Nivolumab Combination Therapy in Advanced Esophageal ... At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both ...