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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 weeks

Awards & highlights

NF110 Trial Summary

This trial will test a new drug, crizotinib, on people with Neurofibromatosis Type 2 who have a progressive vestibular schwannoma. The drug will be taken orally, continuously, for 28 days at a time, for up to 12 cycles.

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.Check my eligibility

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.See study design

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.

NF110 Trial 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.

NF110 Trial 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

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Volumetric Response Rate

Side effects data

From 2020 Phase 3 trial • 207 Patients • NCT01639001

55%

White blood cell count decreased

50%

Nausea

49%

Anaemia

46%

Vomiting

45%

Alanine aminotransferase increased

37%

Neutropenia

35%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

33%

Decreased appetite

27%

Constipation

27%

Platelet count decreased

24%

Cough

21%

Haemoglobin decreased

20%

Leukopenia

17%

Chest pain

17%

Fatigue

16%

Blood albumin decreased

16%

Hyponatraemia

15%

Pyrexia

13%

Back pain

11%

Dizziness

11%

Dyspnoea

11%

Alopecia

10%

Thrombocytopenia

10%

Asthenia

Diarrhoea

Headache

Insomnia

Red blood cell count decreased

Phlebitis

Visual impairment

Upper respiratory tract infection

Nasopharyngitis

Hypoalbuminaemia

Haemoptysis

Pruritus

Rash

Hypokalaemia

Lymphocyte count decreased

Blood bilirubin increased

Pain in extremity

Abdominal distension

Pain

Productive cough

Oedema peripheral

Musculoskeletal pain

Arthralgia

Vision blurred

Chest discomfort

Blood alkaline phosphatase increased

Gamma-glutamyltransferase increased

Paraesthesia

Hypocalcaemia

Abdominal pain

Protein total decreased

Abdominal pain upper

Hypoaesthesia

Pleural effusion

Disease progression

Death

Blood creatinine increased

Pneumonia

Oedema

Blood lactate dehydrogenase increased

Hypoproteinaemia

Hypertension

Pericardial effusion

Syncope

Transaminases increased

Cerebral infarction

100%

80%

60%

40%

20%

Study treatment Arm

Chemotherapy

Crizotinib

NF110 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

~2370

0 / 4Eligibility 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.