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Tyrosine Kinase Inhibitor

Targeted Therapy for Neurofibromatosis (INTUITT-NF2 Trial)

Phase 2

Recruiting

Led By Scott Plotkin, MD

Research Sponsored by Scott R. Plotkin, MD, PhD

Eligibility Criteria Checklist

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

Must have

Female patients must meet specific contraceptive requirements

Male patients must meet specific contraceptive requirements

Must not have

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, brigatinib, to see if it is effective in treating patients with NF2 who have progressive tumors of VS, non-VS, meningiomas, and ependymomas.

Who is the study for?

This trial is for individuals with neurofibromatosis type 2 (NF2) and related progressive tumors like vestibular schwannomas, meningiomas, or ependymomas. Participants must be at least 12 years old, weigh over 40 kg, have a pathogenic NF2 gene variant or meet specific diagnostic criteria, and have measurable disease progression within the last three years. They should not need tumor treatment within six months of joining and must agree to use contraception.

What is being tested?

The INTUITT-NF2 study is testing Neratinib and Brigatinib in separate substudies to see their effects on different types of tumors associated with NF2. It's a phase II trial where patients are given one of these drugs to measure their impact on tumor growth.

What are the potential side effects?

Potential side effects may include digestive issues such as diarrhea, liver problems like elevated enzymes, heart issues including high blood pressure or abnormal heartbeat, lung complications such as shortness of breath or coughing, muscle pain or weakness, skin rash or itching.

Eligibility Criteria

Inclusion Criteria

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

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I am following the required birth control measures.

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I am following the required contraceptive measures.

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I am mostly able to care for myself and carry out daily activities.

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I have a confirmed NF2 diagnosis or a pathogenic NF2 gene variant.

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I have a family history of NF2 and specific related health conditions.

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My NF2-related tumor cannot be removed with surgery.

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I am 12 years or older and weigh at least 40 kg.

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I have a confirmed NF2 gene mutation or meet the NIH/Manchester criteria for NF2.

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My cancer can be measured by MRI.

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I am 12 years old or older.

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I have a tumor related to NF2 that cannot be surgically removed.

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I have NF2, shown by tumors on my hearing nerves or a family history plus specific symptoms.

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I am 12 years or older and weigh at least 40 kg.

Exclusion Criteria

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

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I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

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I am currently taking medication for epilepsy.

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I have serious heart problems that are not under control.

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I have a condition that affects how my body absorbs medication taken by mouth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Radiographic response rate (for each drug substudy)

Secondary study objectives

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability

Side effects data

From 2021 Phase 3 trial • 275 Patients • NCT02737501

57%

Diarrhoea

50%

Blood Creatine Phosphokinase Increased

36%

Cough

32%

Hypertension

32%

Nausea

26%

Back Pain

26%

Aspartate Aminotransferase Increased

23%

Headache

23%

Dyspnoea

23%

Alanine Aminotransferase Increased

23%

Lipase Increased

22%

Vomiting

21%

Fatigue

21%

Pruritus

20%

Arthralgia

19%

Constipation

18%

Rash

17%

Dizziness

15%

Muscle Spasms

15%

Pyrexia

13%

Upper Respiratory Tract Infection

13%

Abdominal Pain

13%

Blood Alkaline Phosphatase Increased

13%

Asthenia

12%

Decreased Appetite

11%

Dyspepsia

11%

Musculoskeletal Pain

10%

Insomnia

10%

Dermatitis Acneiform

10%

Myalgia

10%

Oedema Peripheral

10%

Blood Cholesterol Increased

10%

Oropharyngeal Pain

Productive Cough

Nasopharyngitis

Anaemia

Paraesthesia

Stomatitis

Musculoskeletal Chest Pain

Non-Cardiac Chest Pain

Abdominal Pain Upper

Urinary Tract Infection

Bradycardia

Epistaxis

Pneumonia

Pain In Extremity

Rash Erythematous

Dry Skin

Rash Maculo-Papular

Dysphonia

Electrocardiogram Qt Prolonged

Dry Mouth

Eczema

Blood Creatinine Increased

Sinus Bradycardia

Respiratory Tract Infection

Hyperglycaemia

Hypokalaemia

Hypercholesterolaemia

Vision Blurred

Blood Lactate Dehydrogenase Increased

Hypophosphataemia

Rhinorrhoea

Malaise

Depression

Dysgeusia

Influenza Like Illness

Peripheral Swelling

Gamma-Glutamyltransferase Increased

Neoplasm Progression

Neutrophil Count Decreased

Pulmonary Embolism

Pleural Effusion

Interstitial Lung Disease

Hypocalcaemia

Hypoaesthesia

Taste Disorder

Hypotension

Gastroenteritis

Transaminases Abnormal

Femoral Neck Fracture

Toxicity To Various Agents

Lower Respiratory Tract Infection

Appendicitis

Visual Impairment

Disseminated Intravascular Coagulation

Confusional State

Cerebrovascular Accident

Dysarthria

Encephalopathy

Peripheral Sensory Neuropathy

Cholestasis

Muscular Weakness

Malignant Pleural Effusion

Cancer Pain

Diffuse Large B-Cell Lymphoma

Invasive Breast Carcinoma

Lung Neoplasm Malignant

Ovarian Cancer Stage I

Neutropenia

Gout

Syncope

Seizure

Memory Impairment

Vocal Cord Paralysis

Pericardial Effusion

Cardiac Tamponade

Acute Myocardial Infarction

Angina Pectoris

Arrhythmia

Pneumonitis

Pneumonia Aspiration

Pneumothorax

Pulmonary Oedema

Dysphagia

Inguinal Hernia

Neutropenic Colitis

Oesophageal Obstruction

Cholecystitis

Bile Duct Stone

Multiple Organ Dysfunction Syndrome

Sudden Death

C-Reactive Protein Increased

Fall

Ligament Rupture

Hypoalbuminaemia

Viral Infection

Metastases To Meninges

Lung Adenocarcinoma

Squamous Cell Carcinoma Of Skin

Hypoglycaemia

Delirium

Balance Disorder

Partial Seizures

Atrial Fibrillation

Hepatocellular Injury

Acute Kidney Injury

Photopsia

Metastases To Central Nervous System

Hyperkalaemia

Cognitive Disorder

Gastric Haemorrhage

Mucosal Inflammation

Gastrooesophageal Reflux Disease

Respiratory Distress

100%

80%

60%

40%

20%

Study treatment Arm

Randomized Phase: Brigatinib 90 mg QD/180 QD

Randomized Phase: Crizotinib 250 mg BID

Crossover Phase: Brigatinib 90 mg QD/180 mg QD

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

Group I: Sub-study B (neratinib)Experimental Treatment1 Intervention

The first three participants treated in this arm will receive neratinib 200 mg mg by mouth daily. If these participants tolerate the medication well, subsequent participants will receive neratinib 240 mg by mouth daily.

Group II: Sub-study A (brigatinib) - CLOSED TO ENROLLMENTExperimental Treatment1 Intervention

Subjects treated in this arm will receive brigatinib 90 mg by mouth daily for 7 days and then increased to 180 mg by mouth daily if the drug is tolerated.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Neratinib

2014

Completed Phase 2

~1970

Brigatinib

2019

Completed Phase 3

~1240