Study of Aspirin in Patients With Vestibular Schwannoma

Study Overview
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Brief Summary
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This is a phase II prospective, randomized, double-blind, longitudinal study evaluating whether the administration of aspirin can delay or slow tumor growth and maintain or improve hearing in VS patients.

Detailed Description
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This is a phase II prospective, randomized, double-blind, longitudinal study evaluating whether the administration of aspirin can delay or slow tumor growth and maintain or improve hearing in VS patients. In the Randomized Treatment Phase, patients aged 12 years or older with VSs will be identified and recruited into one of two randomized groups who receive either 1) 325 mg aspirin twice daily (81 mg aspirin twice daily for pediatric patients <50 kg); or 2) a placebo. Patients will stay on aspirin/placebo as long as there is no more than 20% increase in VS volume. At tumor progression, patients will enter the Open Label Follow Up Phase. Patients who progress on placebo will be given the option to receive unblinded aspirin and will be followed until further progression, receiving a definitive treatment (e.g, surgery or radiation), or 42 months post-baseline, whichever occurs first. Patients who progress on aspirin (either blinded or unblinded) will be taken off study drug and followed until they receive a definitive treatment (e.g., surgery or radiation) or reach 42 months post-baseline, whichever comes first.

Official Title
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Prospective, Randomized, Placebo-Controlled Phase II Trial of Aspirin for Vestibular Schwannomas

Conditions
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Vestibular Schwannoma, Acoustic Neuroma, Neurofibromatosis 2

Intervention / Treatment
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* Drug: Aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiographic diagnosis of vestibular schwannoma (NF2-associated or sporadic). Age≥12 years. Ability to provide informed consent.Pediatric patients must provide assent in addition to their parents'/guardians' consent. Adult patients who cannot consent for themselves will not be eligible to participate in this study. Ability to swallow tablets. Exclusion Criteria: Inability to perform volumetric measurements of vestibular schwannoma(s). Inability to tolerate MRI with contrast. Daily use of aspirin within the last two months. Occasional use of aspirin for pain relief is not exclusionary. Known allergy to aspirin. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of aspirin. Pregnant or lactating women. Patients with serious medical illnesses (e.g. severe asthma) that in the option of the investigator could prevent participation in the trial. Active bleeding diathesis. Hydrocephalus from brainstem compression. Febrile illness or flu-like illness in children and adolescents less than 18 years of age.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In the Randomized Treatment Phase, patients aged 12 years or older with VSs will be identified and recruited into one of two randomized groups who receive either 1) 325 mg aspirin twice daily (81 mg aspirin twice daily for pediatric patients <50 kg); or 2) a placebo. Patients will stay on aspirin/placebo as long as there is no more than 20% increase in VS volume. At tumor progression, patients will enter the Open Label Follow Up Phase. Patients who progress on placebo will receive unblinded aspirin. Patients who progress on aspirin (either blinded or unblinded) will be taken off study drug and followed. All patients will be followed for at least 3.5 years after randomization.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin<br>Patients on the experimental arm will receive blinded aspirin. Pediatric subjects who weigh less than 110 lbs will take 81mg aspirin twice a day. All other subjects will take 325mg aspirin twice a day. | Drug: Aspirin<br>* Twice daily aspirin<br>* Other names: Bayer;|
| Placebo Comparator: Placebo<br>Patients on the placebo arm will receive blinded placebo and take it twice a day. | Drug: Placebo<br>* Twice daily placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression Free Survival (PFS) is the length of time from start of study treatment to tumor growth of more than 20%. | Progression, or around 3.5 years |