What side effects are associated with this type of intervention?

The most common treatments for Neurofibromatosis, particularly those involving Tyrosine Kinase Inhibitors like Crizotinib, often include side effects such as diarrhea, mild adverse events, and cutaneous toxicity. In clinical trials, Crizotinib was generally well-tolerated with no serious adverse events reported, and the majority of side effects were mild. Other similar treatments may also cause gastrointestinal issues, skin rashes, and neutropenia.

What prior FDA approvals exist?

The FDA has approved selumetinib, a MEK inhibitor, for the treatment of Neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas. Selumetinib is a targeted therapy similar to Crizotinib, as both are kinase inhibitors, though they target different pathways. Crizotinib, a TKI, is currently being studied for its efficacy in treating progressive vestibular schwannomas in Neurofibromatosis type 2 (NF2).

What other types of research exist?

Promising novel alternatives to Crizotinib for Neurofibromatosis patients include Afatinib, which targets EGFR-mediated signaling and has shown efficacy in neuroblastoma, and other emerging targeted therapies such as seribantumab, which is in clinical trial development for NRG1 fusions. Additionally, ongoing research into PI3K and MEK inhibitors may provide new options.

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Tyrosine Kinase Inhibitor

Crizotinib for Acoustic Neuroma (NF110 Trial)

Phase 2

Waitlist Available

Research Sponsored by University of Alabama at Birmingham

Eligibility Criteria Checklist

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

Must have

Lansky/Karnofsky performance status ≥ 60

Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene

Must not have

Use of drugs that are CYP3A4 substrates with narrow therapeutic indices

Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 weeks

Awards & highlights

No Placebo-Only Group

Summary

This trial tests crizotinib, an oral medication, in patients with NF2 and growing vestibular schwannoma tumors. The drug works by blocking proteins that help the tumor grow.

Who is the study for?

This trial is for children and adults over 6 years old with Neurofibromatosis Type 2 (NF2) and growing vestibular schwannomas. Participants must have stable neurologic symptoms, meet specific health criteria, not be on certain drugs or treatments that could interfere, and women of childbearing age must use effective birth control.

What is being tested?

The trial tests Crizotinib, an oral medication given in continuous 28-day cycles up to a maximum of 12 cycles. It aims to see if it can stop the growth of tumors in patients with NF2 until either the disease progresses further or side effects become too severe.

What are the potential side effects?

Possible side effects include issues from drug interactions due to Crizotinib's effect on liver enzymes, gastrointestinal problems affecting how well the body absorbs the drug, heart rhythm changes, and general risks associated with taking anticancer medications.

Eligibility Criteria

Inclusion Criteria

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

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I can care for myself but may need occasional help.

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I have been diagnosed with neurofibromatosis 2 according to NIH, Manchester criteria, or a genetic test.

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My organ and bone marrow functions are within normal ranges.

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I have a growing tumor on my hearing nerve that can be measured.

Exclusion Criteria

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

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I am taking medication that is sensitive to changes in my body's enzyme levels.

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I am not pregnant, breastfeeding, and if capable of having children, I am using effective birth control.

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I am a man and will not use contraception during the study and for 3 months after.

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I have a stomach or intestine condition that affects how my body absorbs medication.

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I am not using any strong CYP3A4 inhibitor medications or foods.

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My cancer is quickly getting worse and I need steroids for brain or spine tumor symptoms.

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I do not have serious heart rhythm problems or uncontrolled atrial fibrillation.

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I am not taking any strong medications that affect liver enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 48 weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Volumetric Response Rate

Side effects data

From 2020 Phase 3 trial • 207 Patients • NCT01639001

66%

Alanine aminotransferase increased

61%

Diarrhoea

60%

Aspartate aminotransferase increased

59%

Vomiting

54%

Nausea

41%

White blood cell count decreased

40%

Visual impairment

38%

Neutrophil count decreased

36%

Constipation

32%

Cough

28%

Headache

27%

Dizziness

26%

Oedema peripheral

26%

Decreased appetite

25%

Blood albumin decreased

21%

Pain in extremity

21%

Nasopharyngitis

20%

Neutropenia

19%

Anaemia

18%

Pyrexia

18%

Hypoalbuminaemia

17%

Upper respiratory tract infection

15%

Chest pain

15%

Dyspnoea

14%

Disease progression

14%

Blood lactate dehydrogenase increased

13%

Blood creatine phosphokinase increased

13%

Sinus bradycardia

13%

Vision blurred

13%

Gamma-glutamyltransferase increased

13%

Back pain

13%

Insomnia

13%

Protein total decreased

13%

Hypocalcaemia

12%

Rash

12%

Leukopenia

12%

Hypokalaemia

11%

Abdominal distension

10%

Abdominal pain

10%

Blood alkaline phosphatase increased

10%

Pain

10%

Alopecia

Chest discomfort

Blood creatinine increased

Fatigue

Oedema

Hypoaesthesia

Asthenia

Lymphocyte count decreased

Arthralgia

Abdominal pain upper

Platelet count decreased

Hypertension

Haemoptysis

Face oedema

Photopsia

Toothache

Haemoglobin decreased

Paraesthesia

Muscular weakness

Taste disorder

Bradycardia

Pneumonia

Blood creatine phosphokinase MB increased

Hyponatraemia

Hypoproteinaemia

Musculoskeletal pain

Red blood cell count decreased

Productive cough

Blood bilirubin increased

Pruritus

Thrombocytopenia

Pulmonary embolism

Dysphagia

Interstitial lung disease

Death

Pleural effusion

Pneumothorax

Subcutaneous emphysema

Hepatic function abnormal

Abdominal discomfort

Intestinal obstruction

Pancreatitis

Pancreatitis acute

Anaphylactic shock

Impaired healing

Phlebitis

Drug-induced liver injury

Gastrointestinal viral infection

Lower respiratory tract infection

Goitre

Ocular hypertension

Post procedural infection

Deep vein thrombosis

Cellulitis

Hyperuricaemia

Colon adenoma

Adenomyosis

Circulatory collapse

Fracture

Altered state of consciousness

100%

80%

60%

40%

20%

Study treatment Arm

Crizotinib

Chemotherapy

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: Open Label Continuous TreatmentExperimental Treatment1 Intervention

Subjects with Neurofibromatosis Type 2 (NF2) and progressive vestibular schwannoma (VS) will be treated with crizotinib administered orally. Crizotinib will be taken continuously until disease progression or unacceptable toxicity, in continuous treatment cycles of 28 days each, for a maximum of 12 cycles. Clinical response will be assessed by MRI (volumetrics, primary objective) and audiology at the end of every 3rd cycle. Subjects with volumetric tumor progression will be taken off protocol. Patients who complete 12 cycles of treatment without disease progression, but within the following 24 weeks show subsequent disease progression (defined as \>20% increase in target tumor volume compared to off-treatment volume), will be eligible for re-treatment on study for up to 48 additional weeks, provided they still meet study eligibility criteria.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Crizotinib

2014

Completed Phase 3

~2960

0 / 12Eligibility 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

Common treatments for Neurofibromatosis, particularly Neurofibromatosis Type 2 (NF2), include Tyrosine Kinase Inhibitors (TKIs) such as Crizotinib. TKIs work by inhibiting the activity of specific enzymes (tyrosine kinases) that are involved in the signaling pathways promoting tumor growth and survival. By blocking these enzymes, TKIs can reduce tumor growth and potentially shrink existing tumors. This is particularly important for NF2 patients, who often develop multiple benign tumors that can cause significant morbidity due to their location, such as vestibular schwannomas affecting hearing and balance. Effective inhibition of these pathways can help manage tumor progression and improve quality of life for these patients.

Efficacy and Safety of First-Line Treatment Strategies for Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Bayesian Network Meta-Analysis.Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy.Efficacy of treatment for acneiform eruptions related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC): A protocol of systematic review and network meta-analysis.