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Checkpoint Inhibitor

Ipilimumab + Nivolumab + Radiation for Glioblastoma

Phase 2 & 3

Waitlist Available

Led By Andrew B Lassman

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

MGMT promoter without methylation confirmed by central pathology review

IDH mutation testing with no mutation found

Must not have

Prior invasive malignancy within 2 years

Current or planned therapy with warfarin

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether adding immunotherapy to radiation therapy can help people with newly diagnosed glioblastoma that has an unmethylated MGMT.

Who is the study for?

Adults with newly diagnosed MGMT unmethylated glioblastoma who've had surgery can join. They need a good performance status, no prior tumor treatments except resection, and no history of severe allergies to the drugs being tested or other cancers in the last 2 years. Women must not be pregnant and participants should use contraception.

What is being tested?

The trial is testing if combining radiation therapy with immunotherapy drugs Ipilimumab and Nivolumab improves outcomes compared to the usual treatment of radiation therapy plus Temozolomide for this type of brain cancer. It's looking at whether these new drugs help patients live longer without their tumor growing back.

What are the potential side effects?

Ipilimumab and Nivolumab might cause immune-related side effects like inflammation in various organs, skin reactions, hormone gland problems (like thyroid), fatigue, and flu-like symptoms. Temozolomide may lead to nausea, hair loss, tiredness, constipation or diarrhea.

Eligibility Criteria

Inclusion Criteria

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

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My cancer's MGMT gene is not methylated as confirmed by a specialized lab.

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My cancer does not have an IDH mutation.

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I am 18 years old or older.

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My glioblastoma diagnosis has been confirmed by a specialized review.

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I am able to care for myself but may not be able to do active work.

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My cancer does not have an IDH mutation.

Exclusion Criteria

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

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I have not had any other cancer besides this one in the last 2 years.

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I am currently taking or will start taking warfarin.

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I have or had an autoimmune disease that could come back.

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My cancer has spread outside the brain.

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I have had treatment for my tumor, but only surgery.

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I have been diagnosed with HIV or AIDS.

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I have had radiotherapy or other treatments before.

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I do not have current severe digestive system problems.

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I am not pregnant or nursing.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization to two years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization to two years

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization to two 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

Overall Survival (OS) (Phase III)

Progression-free Survival (PFS) (Phase II)

Secondary study objectives

Change in MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) at Six Months (Patient Reported Outcomes)

Number of Participants by Highest Grade Adverse Event Reported

Overall Survival at 2 Years

+2 more

Other study objectives

MGMT Protein Expression

Tumor Biomarker Analyses

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

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (radiation therapy, ipilimumab, nivolumab)Experimental Treatment6 Interventions

Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks. Starting on the first day of radiation, patients also receive ipilimumab IV over 90 minutes Q4W for 4 doses and nivolumab IV over 30 minutes every 2 weeks until disease progression. Patients also undergo contrast-enhanced brain MRI throughout the trial.

Group II: Arm I (radiation therapy, temozolomide)Active Control6 Interventions

Patients undergo radiation therapy for 5 days per week (Monday-Friday) for a total of 30 fractions over 6 weeks and simultaneously receive temozolomide PO daily for 6 weeks. After radiation, patients may wear the Optune device at the discretion of the patient and their treating physician. Beginning 1 month after radiation therapy, patients receive temozolomide on days 1-5. Treatment repeats every 28 days for up to 12 cycles at the discretion of the treating investigator in the absence of disease progression or unacceptable toxicity. Patients also undergo contrast-enhanced brain MRI throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Contrast-enhanced Magnetic Resonance Imaging

2005

Completed Phase 1

~320

Ipilimumab

2015

Completed Phase 3

~3420