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Checkpoint Inhibitor

Intravenous and Intrathecal Nivolumab for Leptomeningeal Disease

Phase 1

Recruiting

Led By Isabella C Glitza

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

Patients must have radiographic and/or CSF cytological evidence of LMD

Patients with lung cancer must have non-small cell lung cancer

Must not have

Patients who have ongoing > grade 2 adverse event (AE) side effects of alpha-PD-1 and/or anti-CTLA-4 therapy

Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing a combination of two immunotherapy drugs to see if they can better treat leptomeningeal disease with fewer side effects than current treatments.

Who is the study for?

This trial is for adults with leptomeningeal disease from melanoma or non-small cell lung cancer. Participants can have had prior treatments but must meet specific conditions, such as not having severe allergies to monoclonal antibodies, no active autoimmune diseases requiring treatment in the past 2 years, and no ongoing serious side effects from previous immunotherapy.

What is being tested?

The trial tests intrathecal (into the spinal canal) and intravenous Nivolumab to see how well it works against leptomeningeal disease. It aims to find the best dose and assess side effects when using this form of immunotherapy that helps the immune system fight cancer.

What are the potential side effects?

Potential side effects include reactions related to infusion, immune-related inflammation in various organs, fatigue, possible worsening of pre-existing autoimmune diseases, increased risk of infections due to immune system changes caused by Nivolumab.

Eligibility Criteria

Inclusion Criteria

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

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My tests show cancer cells in my brain or spinal fluid.

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My lung cancer is non-small cell type.

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I can take care of myself but might not be able to do heavy physical work.

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I have been diagnosed with melanoma in the brain or its metastasis.

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I am 18 years old or older.

Exclusion Criteria

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

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I am experiencing significant side effects from my immunotherapy.

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I haven't had any live vaccines in the last 12 weeks.

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I haven't taken steroids or immunosuppressants in the last 14 days.

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I am currently undergoing cancer treatment or participating in a drug trial.

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I have had pneumonitis before.

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

Incidence of adverse events

Recommended dose of combined intrathecal (IT) and intravenous (IV) nivolumab defined as the highest dose for which the posterior probability of toxicity is closest to 30% (dose escalation part)

Secondary study objectives

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

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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: Treatment (nivolumab)Experimental Treatment6 Interventions

Patients receive nivolumab IT over 5 minutes on day 1 of every cycle. Beginning in cycle 2, patients also receive nivolumab IV over 30 minutes on day 1 (4 hours after the IT dose). Cycles repeat every 14 days for 18 cycles and then every 28 days (cycles 19 and beyond) in the absence of disease progression or unacceptable toxicity. Patients will have CSF and blood specimen collection on days 1, 2, 8 of each cycle and end of treatment. Patients undergo CT or PET at baseline, cycle 5 and then every 8 weeks. Patients undergo MRI at baseline, cycles 3, 5, and then every 8 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740