Medical Treatment of "High-Risk" Neurofibromas

Phase 2

Completed

• Conditions: Neurofibromatosis 1
• Interventions: Drug: Peg-Interferon alpha-2b; Drug: Celecoxib (Celebrex); Drug: Temozolomide (temodar); Drug: Vincristine Sulfate (Oncovin)

• Registration Number: NCT00846430
• Lead Sponsor: Spectrum Health Hospitals

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.

Study Timeline

• Study Start: 2008-10
• Study First Submitted: 2009-01-16
• Study First Submitted QC: 2009-02-16
• Study First Posted: 2009-02-18
• Primary Completion: 2017-04
• Study Completion: 2017-05
• Results First Submitted: 2023-07-11
• Status Verified: 2023-08
• Results First Submitted QC: 2023-08-07
• Last Update Submitted: 2023-08-07
• Results First Posted: 2023-08-30
• Last Update Posted: 2023-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-Label Intervention	Peg-Interferon alpha-2b	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.
Open-Label Intervention	Celecoxib (Celebrex)	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.
Open-Label Intervention	Temozolomide (temodar)	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.
Open-Label Intervention	Vincristine Sulfate (Oncovin)	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.

Primary Outcome Measures

Name	Time	Method
Improvement of Symptoms and Pain	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	Monthly physical exam first three months and then every three months after, for up to 36 months
Response by MRI Measurements	evaluated 6, 12 and 24 months compared to baseline	partial response by RICST criteria is defined as \>50% tumor shrinkage

Secondary Outcome Measures

Name	Time	Method
No Reported Psychological Toxicity Based Upon Psychological Evaluations	Psychological evaluation at 24 months	Psychological toxicity defined as suicidal ideation

Trial Locations

Locations (1)

Helen DeVos Children's Hospital; 🇺🇸 Grand Rapids, Michigan, United States