What side effects are associated with this type of intervention?

Common treatments for malignant glioma include radiotherapy, chemotherapy, and immunotherapy such as PD-1 inhibitors like nivolumab. Radiotherapy can cause acute and subacute radiation encephalopathy, leading to headaches, focal neurologic symptoms, and nausea. Chemotherapeutic agents like temozolomide are associated with headaches in about 20% of patients, and intrathecal methotrexate can cause aseptic meningitis. Immunotherapy with PD-1 inhibitors, such as nivolumab, can lead to immune-related adverse events including pneumonitis, colitis, hepatitis, and endocrinopathies. These treatments aim to manage the tumor but come with a range of potential side effects that need to be carefully monitored.

What prior FDA approvals exist?

The FDA has approved several treatments for malignant glioma, with a focus on immunotherapy. Nivolumab, a PD-1 inhibitor, is being studied for its efficacy in treating recurrent or progressive high-grade glioma. This aligns with the broader trend of using immunotherapy, such as monoclonal antibodies, to enhance the body's immune response against tumor cells. While specific FDA approvals for malignant glioma treatments similar to nivolumab are not detailed in the provided context, the use of PD-1 inhibitors represents a significant advancement in the therapeutic landscape for this condition.

What other types of research exist?

Promising alternatives to Nivolumab for Malignant Glioma patients include Pembrolizumab, which has shown some potential in increasing progression-free survival (PFS) and overall survival (OS) in a small randomized surgical study. Additionally, ongoing research into biomarkers of response and combination therapies with immune checkpoint inhibitors may offer new treatment avenues. Further studies are needed to validate these findings and identify effective combinations.

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Checkpoint Inhibitor

Immunotherapy Before and After Surgery for Brain Tumor

Q: What is the mechanism of action of this treatment?

The most common treatments for Malignant Glioma, particularly immunotherapy agents like nivolumab, work by inhibiting the programmed cell death protein 1 (PD-1) pathway. PD-1 is a checkpoint protein on immune cells that, when engaged, dampens the immune response. Tumor cells often exploit this pathway to evade immune detection. Nivolumab blocks PD-1, thereby enhancing the body's immune response against tumor cells. This mechanism is crucial for Malignant Glioma patients as it offers a targeted approach to boost the immune system's ability to recognize and destroy cancer cells, potentially leading to better control of tumor growth and improved survival outcomes.

Phase 1

Recruiting

Research Sponsored by Sabine Mueller, MD, PhD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have evidence of recurrence or progression of disease by MRI scan

Age: Participants must be > 6 months and < 25 years of age at time of enrollment

Must not have

Has an active infection requiring systemic therapy

Has known history of, or any evidence of active non-infectious pneumonitis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the effects of nivolumab, an immunotherapy drug, in children and young adults with severe brain cancer that has returned or worsened. The drug helps the immune system fight the cancer and may prevent it from growing.

Who is the study for?

This trial is for children and young adults aged 6 months to less than 22 years with high-grade gliomas (brain tumors) that have recurred or progressed. They must have recovered from previous cancer treatments, meet specific blood count and organ function criteria, be candidates for surgical tumor removal, and not be on certain medications or have conditions like active TB or autoimmune diseases.

What is being tested?

The trial tests the safety of nivolumab and ipilimumab immunotherapies before and after surgery in patients with aggressive brain tumors. These drugs are designed to help the immune system fight cancer by blocking pathways that allow tumor cells to evade an immune response.

What are the potential side effects?

Potential side effects include inflammation in various organs, infusion reactions similar to allergic responses, fatigue, digestive issues such as diarrhea or constipation, skin rash, hormone gland problems (like thyroid dysfunction), liver inflammation, and potential worsening of pre-existing autoimmune diseases.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My MRI shows my disease is getting worse.

Select...

I am between 6 months and 25 years old.

Select...

My surgery aims to remove as much of the tumor as possible, not just to diagnose.

Select...

I have had high-grade brain cancer treated with radiation or chemotherapy.

Select...

I agree to only use the study's treatment and no other cancer-killing therapies while participating.

Select...

I have a high-grade brain tumor and am eligible for surgery to remove it.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently being treated for an infection with medication.

Select...

I have or had lung inflammation not caused by an infection.

Select...

I have an autoimmune disease treated with medication in the last 2 years.

Select...

I have had a stem cell transplant from a donor.

Select...

I have an active tuberculosis infection.

Select...

My cancer has spread widely in my brain or body.

Select...

My tumor is mainly in my brainstem or spinal cord.

Select...

I have been diagnosed with an immune system disorder.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage change in cell cycle-related genetic signature

Therapeutic procedure

Secondary study objectives

Overall survival

Progression-free survival (PFS)

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Neoadjuvant nivolumab and adjuvant nivolumabExperimental Treatment3 Interventions

NEOADJUVANT: Patients receive nivolumab IV over 30 minutes 14 days before undergoing standard of care surgical resection. ADJUVANT MAINTENANCE: After completion of neoadjuvant infusion, patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Malignant Glioma, particularly immunotherapy agents like nivolumab, work by inhibiting the programmed cell death protein 1 (PD-1) pathway. PD-1 is a checkpoint protein on immune cells that, when engaged, dampens the immune response. Tumor cells often exploit this pathway to evade immune detection. Nivolumab blocks PD-1, thereby enhancing the body's immune response against tumor cells. This mechanism is crucial for Malignant Glioma patients as it offers a targeted approach to boost the immune system's ability to recognize and destroy cancer cells, potentially leading to better control of tumor growth and improved survival outcomes.