Medical Treatment of "High-Risk" Neurofibromas

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

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.

Study Overview

• Status: Completed
• Conditions: Neurofibromatosis 1
• Intervention / Treatment: Drug: Peg-Interferon alpha-2b; Drug: Celecoxib (Celebrex); Drug: Temozolomide (temodar); Drug: Vincristine Sulfate (Oncovin)

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 Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 26 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Peg-Interferon alpha-2b; age and weight dependant; Drug: Celecoxib (Celebrex); age and weight dependant; Drug: Temozolomide (temodar); age and weight dependant; Drug: Vincristine Sulfate (Oncovin); age and weight dependant

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Investigators: Principal Investigator: Albert S Cornelius, MD, Helen DeVos Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2008
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: January 16, 2009
• First Submitted That Met QC Criteria: February 16, 2009
• First Posted (Estimated): February 18, 2009

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Celecoxib; Temozolomide; Temodar; Oncovin; Neurofibromatosis 1; Neurofibromas; Celebrex; Peg-Interferon alpha-2b; PEG-Intron; Vincristine Sulfate
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Cyclooxygenase 2 Inhibitors; Interferons; Interferon-alpha; Temozolomide; Interferon alpha-2; Celecoxib; Vincristine; Peginterferon alfa-2b
• Other Study ID Numbers: 2008-260 (Other Identifier: Spectrum Health)