Nivolumab for Brain Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests nivolumab, an immunotherapy drug, to determine if it can shrink rare brain or spine tumors or slow their growth. The trial aims to stimulate the immune system to combat these tumors, which have few proven treatments due to their rarity. It suits individuals whose rare brain or spine tumor has returned after standard treatments. Participants receive nivolumab through an IV every two weeks and undergo regular monitoring with MRIs and blood tests. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that nivolumab is likely to be safe for humans?

Research has shown that nivolumab is generally safe for humans. Studies have specifically examined its use in brain cancer patients. For instance, one study found that nivolumab could reach brain tumors and start working in about a week, suggesting it can effectively target brain cancer. Another study on glioblastoma, a type of brain cancer, confirmed that nivolumab was safe for these patients. The safety findings were based on people who had already used nivolumab for brain cancer treatment, and no major safety issues were reported.

Nivolumab is an immunotherapy drug, meaning it helps the immune system fight cancer. However, it can cause side effects like tiredness, skin rash, or nausea. These side effects are usually manageable. The current study phase indicates that nivolumab's safety is well-understood, but discussing potential side effects with a doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nivolumab is unique because it leverages the body's immune system to target and attack brain cancer cells. Unlike traditional treatments such as chemotherapy and radiation, which directly destroy cancer cells but can also harm healthy tissue, nivolumab is an immune checkpoint inhibitor. It works by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's natural ability to fight the tumor. Researchers are excited because this approach could potentially lead to more targeted and less toxic treatment options for patients with brain cancer.

What evidence suggests that nivolumab might be an effective treatment for brain cancer?

Research has shown that nivolumab, a type of immunotherapy, is under study for its potential to treat brain tumors by helping the immune system attack cancer cells. Studies have found that nivolumab can reach brain tumors, effectively targeting the necessary areas. However, in some trials, such as those for glioblastoma (a type of brain cancer), it did not improve survival compared to other treatments. While nivolumab has been safely used with other therapies, its ability to significantly improve outcomes for rare brain and spinal cord tumors remains under investigation. Early results suggest potential benefits, but more research is needed for confirmation. Participants in this trial will receive nivolumab at a standard dose, as outlined in the trial design. ^{3 4 6 7 8}

Who Is on the Research Team?

Byram H Ozer, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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

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

Women of childbearing potential must use contraception

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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 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]

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]

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]

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]

Citations

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The Safety of Available Immunotherapy for the Treatment of ... Glioblastoma (GBM) is the most common malignant primary brain tumor in adults ... Safety data from published clinical trials, including ongoing clinical ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02529072

Nivolumab With DC Vaccines for Recurrent Brain Tumors This two-arm randomized trial will evaluate the safety of nivolumab in combination with DC vaccinations for the treatment of bevacizumab-naïve subjects with ...