Medical Treatment of "High-Risk" Neurofibromas in Patients With Type 1 Neurofibromatosis: A Clinical Trial of Sequential Medical Therapies
Overview
- Phase
- Phase 2
- Intervention
- Peg-Interferon alpha-2b
- Conditions
- Neurofibromatosis 1
- Sponsor
- Spectrum Health Hospitals
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Improvement of Symptoms and Pain
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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
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.
Investigators
Albert Cornelius
MD
Spectrum Health Hospitals
Eligibility Criteria
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
Arms & Interventions
Open-Label Intervention
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.
Intervention: Peg-Interferon alpha-2b
Open-Label Intervention
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.
Intervention: Celecoxib (Celebrex)
Open-Label Intervention
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.
Intervention: Temozolomide (temodar)
Open-Label Intervention
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.
Intervention: Vincristine Sulfate (Oncovin)
Outcomes
Primary Outcomes
Improvement of Symptoms and Pain
Time Frame: Monthly physical exam first three months and then every three months after, for up to 36 months
Subjects will be evaluated for pain and Quality of Life scores
At Least 50% Shrinkage in Tumor Measurements by Physical Examination
Time Frame: Monthly physical exam first three months and then every three months after, for up to 36 months
Response by MRI Measurements
Time Frame: evaluated 6, 12 and 24 months compared to baseline
partial response by RICST criteria is defined as \>50% tumor shrinkage
Secondary Outcomes
- No Reported Psychological Toxicity Based Upon Psychological Evaluations(Psychological evaluation at 24 months)