Nivolumab for Brain Cancer

Recruiting at 11 trial locations

Overseen By Marta Penas-Prado, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Autoimmune disease, Cardiac issues, 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: 11

Duration: 64 weeks

133 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on a corticosteroid dose greater than physiologic replacement dosing (30 mg of cortisone per day or its equivalent). It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on a corticosteroid dose greater than 30 mg of cortisone per day or its equivalent, and you cannot be receiving any other investigational agents.

What data supports the idea that Nivolumab for Brain Cancer is an effective treatment?

The available research shows that Nivolumab, when used for non-small cell lung cancer (NSCLC) with brain metastases, has shown some positive results. In one study, out of five patients with brain metastases, one had a complete response and another had a partial response in the brain. This suggests that Nivolumab might have some effectiveness in treating brain-related conditions, although more research is needed to confirm its effectiveness specifically for brain cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Nivolumab for brain cancer?

Research shows that Nivolumab, used for lung cancer with brain metastases, has shown some positive effects in the brain, with one complete and one partial response observed in patients. This suggests it might have potential benefits for brain cancer, but more research is needed. ^{1 2 3 4 5}

What safety data exists for Nivolumab in treating brain cancer?

Nivolumab, also known as Opdivo, is associated with immune-related adverse events, including rare cases of encephalitis. Reports indicate that encephalitis occurs in 1% to 3% of treated cases and can be managed with steroids. Neurologic adverse events range from mild headaches to severe encephalitis, which is reversible with prompt treatment. While CNS toxicities are rare, they require early recognition and management to prevent severe outcomes. ^{6 7 8 9 10}

What safety information is available for Nivolumab (Opdivo) in humans?

Nivolumab, also known as Opdivo, is generally safe for many people, but it can cause rare but serious side effects like encephalitis (inflammation of the brain). This condition can lead to symptoms such as confusion and weakness, but it is often treatable with steroids if caught early. ^{6 7 8 9 10}

Is the drug Nivolumab (Opdivo) a promising treatment for brain cancer?

Nivolumab has shown promise in treating certain types of lung cancer and has some activity in brain metastases from melanoma, suggesting it might be a promising option for brain cancer. However, more specific research on brain cancer is needed to confirm its effectiveness. ^{1 11 12 13 14}

How does the drug Nivolumab work differently for brain cancer compared to other treatments?

Nivolumab is unique because it is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, which is different from traditional chemotherapy that directly kills cancer cells. Although it is primarily used for lung cancer, its potential to treat brain cancer is being explored, especially since it may have some ability to affect brain tumors despite the blood-brain barrier. ^{1 11 12 13 14}

What is the purpose of this trial?

Background: More than 130 primary tumors of the central nervous system (CNS) have been identified. Most affect less than 1,000 people in the United States each year. Because these tumors are so rare, there are few proven therapies. This study will test whether the immunotherapy drug nivolumab is an effective treatment for people with rare CNS tumors. Objectives: To learn if stimulating the immune system using the drug nivolumab can shrink tumors in people with rare CNS (brain or spine) tumors or increase the time it takes for these tumors to grow or spread. Eligibility: Adults whose rare CNS tumor has returned. Design: Individuals will be screened: * Heart and blood tests * Physical and neurological exam * Hepatitis tests * Pregnancy test * MRI. They will lay in a machine that takes pictures. * Tumor tissue sample. This can be from a previous procedure. At the start of the study, participants will have blood tests. They will answer questions about their symptoms and their quality of life. Individuals will get nivolumab in a vein every 2 weeks for up to 64 weeks. Individuals will have monthly blood tests. Every other month they will have an MRI and a neurologic function test. They will also answer questions about their quality of life. Genetic tests will be done on individuals' tumor tissue. Individuals will be contacted if any clinically important results are found. After treatment ends, individuals will be monitored for up to 5 years. They will have a series of MRIs and neurological function tests. They will be asked to report any symptoms they experience....

Research Team

Byram H Ozer, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with certain rare brain or spine tumors that have come back can join this trial. They must be over 18, in good health, and not on high steroid doses. Participants need to have had all COVID-19 shots, agree to use birth control if needed, and provide a tumor tissue sample. People who've had other cancers or severe illnesses, are pregnant or breastfeeding, allergic to the drug's ingredients, unable to get MRIs or vaccinated against COVID-19 can't join.

Inclusion Criteria

My diagnosis is one of the listed brain or central nervous system tumors.

Tumor tissue must be available for immunophenotyping by NCI Laboratory of Pathology

My cancer has grown despite treatment.

Exclusion Criteria

History of allergy to study drug components

I have previously received immunotherapy or specific cancer vaccines.

I do not have another cancer that could affect this treatment's safety or results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab intravenously every 2 weeks for cycles 1-2, then every 4 weeks for up to 64 weeks

64 weeks

Bi-weekly visits for first 2 cycles, then monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment with MRIs and neurological function tests

5 years

Every 8 weeks for 1 year, then every 3 months for 1 year, then every 4 months for 1 year, then every 6 months

Treatment Details

Interventions

• Nivolumab

Trial Overview The trial is testing Nivolumab—an immunotherapy drug—given every two weeks through an IV for up to 64 weeks. It aims to see if it shrinks these rare CNS tumors or slows their growth. The study includes regular blood tests, MRIs every two months along with neurological function tests and quality of life surveys.

Participant Groups

Group I: 1/Experimental Therapy Experimental Treatment 1 Intervention

Individuals will receive nivolumab at standard dose of 240 mg IV every 2 weeks for cycles 1 through 2, then doses of 480 mg every 4 weeks for a total of 14 additional doses

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Nivolumab plus ipilimumab significantly improved overall survival in patients with metastatic non-small cell lung cancer (NSCLC), including those with baseline brain metastases, compared to chemotherapy, with a hazard ratio of 0.63 for those with brain metastases and 0.76 for those without.

At 5 years, patients with baseline brain metastases treated with nivolumab plus ipilimumab had higher rates of systemic (12%) and intracranial (16%) progression-free survival compared to chemotherapy (0% and 6%, respectively), and fewer developed new brain lesions (4% vs. 20%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. Reck, M., Ciuleanu, TE., Lee, JS., et al.[2023]

Nivolumab, an anti-PD-1 immunotherapy, was associated with immune-related encephalitis in a 60-year-old woman with recurrent head and neck cancer, highlighting a potential serious side effect of this treatment.

Despite the occurrence of immune-related toxicities, including encephalitis and hypothyroidism, the patient achieved a complete radiologic response one year after stopping nivolumab, demonstrating the efficacy of immunotherapy in managing advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoimmune-related encephalitis during treatment with nivolumab for advanced head and neck cancer: a case report. Guidi, A., Violati, M., Blasi, M., et al.[2022]

In a retrospective study of five patients with advanced non-small cell lung cancer (NSCLC) and new or progressing brain metastases, nivolumab showed promising intracranial activity, with one complete and one partial response observed, and stabilization of leptomeningeal carcinomatosis in another patient.

Nivolumab was well-tolerated, with no severe treatment-related adverse events reported, suggesting a favorable safety profile for patients with CNS metastases from NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. Dudnik, E., Yust-Katz, S., Nechushtan, H., et al.[2022]

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., et al.[2022]

In a phase III trial, nivolumab significantly improved health-related quality of life (HRQoL) and disease-related symptoms compared to docetaxel in patients with advanced non-squamous non-small cell lung cancer, with improvements noted at multiple time points (weeks 12, 24, 30, and 42).

Patients receiving nivolumab experienced a longer time to first deterioration in HRQoL compared to those treated with docetaxel, indicating a more favorable safety profile and sustained symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Reck, M., Brahmer, J., Bennett, B., et al.[2019]

In a review of 3,763 patients with advanced melanoma treated with nivolumab and ipilimumab, 0.93% experienced serious neurologic immune-related adverse events (irAEs), including encephalitis, with a median onset time of 45 days.

Most neurologic irAEs resolved (75% of cases), but awareness and prompt management of these rare but serious events are crucial for oncologists and neurologists to prevent complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. Larkin, J., Chmielowski, B., Lao, CD., et al.[2018]

A case study of a 59-year-old woman with treatment-resistant laryngeal cancer revealed that nivolumab, an immunotherapy drug, can cause severe central nervous system (CNS) toxicities, specifically acute demyelinating encephalitis, which is rarely reported in the literature.

The patient's symptoms improved significantly after discontinuing nivolumab and receiving high-dose steroids and immunoglobulin therapy, suggesting that CNS toxicity from immune checkpoint inhibitors may be reversible with prompt treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. Zafar, Z., Vogler, C., Hudali, T., et al.[2020]

In a study of 47 patients with metastatic renal cell carcinoma treated with nivolumab, 48.9% experienced immune-related adverse events (irAEs), with rash being the most common.

Patients who developed irAEs had significantly longer progression-free survival (13.1 months vs. 4.87 months) and overall survival (26.0 months vs. not reached) compared to those without irAEs, indicating that the presence of irAEs may be a positive prognostic factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. Ishihara, H., Takagi, T., Kondo, T., et al.[2020]

Nivolumab, a widely used chemotherapy drug for various cancers, has well-documented common side effects, but this study highlights the extremely rare occurrence of encephalitis as a side effect.

Reporting rare side effects like encephalitis is crucial as the field of cancer treatment evolves and more chemotherapeutic agents are introduced, ensuring better patient safety and awareness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. Chaucer, B., Stone, A., Demanes, A., et al.[2020]

Nivolumab, an immune checkpoint inhibitor approved for non-small cell lung cancer, can cause rare but serious side effects like immune-related encephalitis in 1% to 3% of patients, highlighting the need for awareness among healthcare providers.

In a case study of a 74-year-old male with stage 4 lung cancer, early recognition and treatment with intravenous steroids led to significant recovery from nivolumab-induced encephalitis, emphasizing the importance of prompt management to reduce risks of severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. Richard, K., Weslow, J., Porcella, SL., et al.[2018]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab and ipilimumab show significant intracranial activity in patients with melanoma brain metastases, with response rates of 46% and 57% in two phase II studies, respectively.

Nivolumab can penetrate the cerebrospinal fluid (CSF), achieving concentrations that are effective for therapeutic action, challenging the belief that large molecules like monoclonal antibodies cannot affect the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. van Bussel, MTJ., Beijnen, JH., Brandsma, D.[2020]

In a study involving 40 newly diagnosed and 86 recurrent glioblastoma patients, PD-L1 blockade with durvalumab did not meet primary efficacy endpoints, indicating it was ineffective in improving outcomes compared to standard treatments.

Recurrent glioblastoma patients exhibited significantly lower levels of circulating immune cell subsets, and the use of dexamethasone was associated with a reduction in these immune cells, suggesting that immune suppression may hinder treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. Nayak, L., Standifer, N., Dietrich, J., et al.[2023]

References

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

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. [2023]

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

Autoimmune-related encephalitis during treatment with nivolumab for advanced head and neck cancer: a case report. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases. [2022]

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

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. [2022]

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

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. [2018]

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

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. [2020]

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

Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. [2020]

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

Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. [2020]

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

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. [2018]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. [2020]

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

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. [2023]