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Checkpoint Inhibitor

Nivolumab + Radiation Therapy +/- Ipilimumab for Brain Metastasis from Lung Cancer

Phase 1 & 2

Waitlist Available

Led By Jing Li

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Have a performance status of 0 or 1 on the ECOG performance scale

Female subjects of childbearing potential should have a negative pregnancy test and be willing to use birth control

Must not have

Recent use of monoclonal antibodies or anti PD1/PD-L1 therapies

Diagnosis of severe active scleroderma, lupus, or other rheumatologic/autoimmune diseases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 month after radiation to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the side effects and best dose of nivolumab when given with stereotactic radiosurgery or whole brain radiotherapy, with or without ipilimumab, to treat patients with non-small cell lung cancer that has spread to the brain.

Who is the study for?

This trial is for adults with non-small cell lung cancer that has spread to the brain. They must have at least one treatable brain lesion, be in good physical condition (ECOG 0 or 1), and meet certain blood and biochemical criteria. Women of childbearing age need a negative pregnancy test and agree to birth control; men must use contraception too. Those who've had prior treatments may qualify under specific conditions.

What is being tested?

The study is testing how well patients respond to Nivolumab combined with either stereotactic radiosurgery or whole-brain radiotherapy, with or without Ipilimumab. It aims to find the safest doses while assessing how these therapies affect tumor growth in the brain from lung cancer.

What are the potential side effects?

Possible side effects include immune-related reactions affecting organs, fatigue, skin issues, hormone gland problems like thyroid dysfunction, infusion reactions during treatment administration, and potential worsening of pre-existing autoimmune diseases.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am not pregnant and agree to use birth control.

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My cancer has spread to my brain, as confirmed by an MRI.

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My lung cancer diagnosis was confirmed through a lab test.

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I have a brain lesion larger than 0.3 cm that can be treated with radiation.

Exclusion Criteria

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

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I have recently used monoclonal antibodies or anti PD1/PD-L1 therapies.

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I have been diagnosed with a severe active form of scleroderma, lupus, or another similar autoimmune disease.

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I have a known infection of HIV, hepatitis B, or hepatitis C.

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I have another cancer that is getting worse, cancer in my brain's coverings, or an active infection.

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I have not had a live vaccine or severe side effects from radiation or brain toxicity recently.

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I cannot or do not want to undergo an MRI of my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 month after radiation to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 month after radiation to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 month after radiation to 3 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

RP2D of nivolumab in combination with ipilimumab defined as the probability of > 15% intracranial or > 30% extracranial DLT (Phase I)

Recommended phase 2 dose (RP2D) of nivolumab defined as the probability of > 15% intracranial or > 30% extracranial dose limiting toxicities (DLT) (Phase I)

Secondary study objectives

Neurocognitive changes assessed by the Hopkins Verbal Learning Revised (HVLT-R) total recall test (Phase II)

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

4Treatment groups

Experimental Treatment

Group I: Group D (nivolumab, ipilimumab, WBRT)Experimental Treatment5 Interventions

GROUP D: Patients receive nivolumab as in Group A and ipilimumab as in Group C. Patients undergo WBRT once daily for 10 days.

Group II: Group C (nivolumab, ipilimumab, SRS)Experimental Treatment5 Interventions

Patients receive nivolumab as in Group A and ipilimumab IV over 90 minutes every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.

Group III: Group B (nivolumab, WBRT)Experimental Treatment4 Interventions

Patients then receive nivolumab as in Group A. Patients undergo WBRT once daily for 10 days.

Group IV: Group A (nivolumab, SRS)Experimental Treatment4 Interventions

Patients receive nivolumab IV over 90 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Stereotactic Radiosurgery

2021

Completed Phase 2

~440

Cognitive Assessment

2011

Completed Phase 2

~1420