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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.
Select...
I am not pregnant or nursing.

Timeline

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%
Cushingoid
10%
Tinnitus
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%
0%
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
2014
Completed Phase 3
~3140
Nivolumab
2014
Completed Phase 3
~5220
Radiation Therapy
2017
Completed Phase 3
~7250

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,868 Previous Clinical Trials
41,010,678 Total Patients Enrolled
142 Trials studying Gliosarcoma
10,593 Patients Enrolled for Gliosarcoma
NRG OncologyOTHER
237 Previous Clinical Trials
102,615 Total Patients Enrolled
9 Trials studying Gliosarcoma
3,392 Patients Enrolled for Gliosarcoma
Andrew B LassmanPrincipal InvestigatorNRG Oncology

Media Library

Ipilimumab (Checkpoint Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04396860 — Phase 2 & 3
Gliosarcoma Research Study Groups: Arm II (radiation therapy, ipilimumab, nivolumab), Arm I (radiation therapy, temozolomide)
Gliosarcoma Clinical Trial 2023: Ipilimumab Highlights & Side Effects. Trial Name: NCT04396860 — Phase 2 & 3
Ipilimumab (Checkpoint Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04396860 — Phase 2 & 3
~31 spots leftby Oct 2025