Medical Treatment of High-Risk Neurofibromas

Study Overview
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Brief Summary
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Patients with neurofibromatosis type 1 (NF1) commonly develop non-cancerous tumors called plexiform neurofibromas. These tumors can be defined as high-risk when they result in severe pain, physical disability, organ dysfunction and/or become life-threatening. Presently, there is no effective medical therapy to offer patients with high-risk plexiform neurofibromas, and surgery does not provide lasting help. This study will evaluate the effectiveness of two treatment combinations in patients with high-risk plexiform neurofibromas.

Detailed Description
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The study's design involves treating eligible patients with a combination of celecoxib and pegylated interferon alpha-2b. If the patients have at least a partial response after six months, they may continue on the same treatment for up to two years. If the patient experiences less than a partial response, or has progressive disease after six months of therapy, then vincristine and temozolomide will be added to the celecoxib and interferon alpha-2b backbone. Response to treatment will be assessed after a minimum of six months, presuming the patient has not experienced progressive disease. Total duration of therapy on study is two years for any individual treatment plan.

Official Title
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Medical Treatment of High-Risk Neurofibromas in Patients With Type 1 Neurofibromatosis: A Clinical Trial of Sequential Medical Therapies

Conditions
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Neurofibromatosis 1

Intervention / Treatment
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* Drug: Peg-Interferon alpha-2b
* Drug: Celecoxib (Celebrex)
* Drug: Temozolomide (temodar)
* Drug: Vincristine Sulfate (Oncovin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High-Risk Plexiform Neurofibromas associated with a diagnosis of NF1 2-30 years old (minimum bodyweight of 10 kilograms) Adequate renal function Exclusion Criteria: Previously untreated active optic glioma History of any previous allergy to study medications History of ischemic vascular disease Pregnancy / Breast feeding

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 30 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-Label Intervention<br>This is a phase II single arm study with sequential treatments available by response where all participants begin therapy with a combination of celecoxib and interferon alpha-2b (CI, treatment-1). Response to CI therapy will be assessed at six months by clinical and radiographic evaluations. Those patients who have achieved a partial response (improvement in pain, improvement in functioning, or ≥50% reduction in tumor size) or complete response (resolution of pain, and normalization of functioning with a ≥ 90% reduction in tumor size) will continue with the same CI therapy for up-to two years on study. | Drug: Peg-Interferon alpha-2b<br>* age and weight dependant<br>Drug: Celecoxib (Celebrex)<br>* age and weight dependant<br>Drug: Temozolomide (temodar)<br>* age and weight dependant<br>Drug: Vincristine Sulfate (Oncovin)<br>* age and weight dependant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Symptoms and Pain | Subjects will be evaluated for pain and Quality of Life scores | Monthly physical exam first three months and then every three months after, for up to 36 months | 
| At Least 50% Shrinkage in Tumor Measurements by Physical Examination |  | Monthly physical exam first three months and then every three months after, for up to 36 months | 
| Response by MRI Measurements | partial response by RICST criteria is defined as >50% tumor shrinkage | evaluated 6, 12 and 24 months compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No Reported Psychological Toxicity Based Upon Psychological Evaluations | Psychological toxicity defined as suicidal ideation | Psychological evaluation at 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurofibromas, Neurofibromatosis 1, Celecoxib, Celebrex, Peg-Interferon alpha-2b, PEG-Intron, Temozolomide, Temodar, Vincristine Sulfate, Oncovin