Pegintron to Treat Plexiform Neurofibromas in Children and Young Adults
Neurofibromatosis 1 (NF1) is a common autosomal dominant neurogenetic disorder characterized by diverse cutaneous, neurological, skeletal and neoplastic manifestations. Approximately 25 percent of individuals with NF1 develop plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. Plexiform neurofibromas may be congenital and appear to have the fastest growth rate in young children. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Interferon-alpha has shown immune modulatory and antiproliferative effects in a variety of malignancies, and also inhibits angiogenesis. The pegylated preparation, peginterferon alfa-2beta (Pegintron) lengthens the plasma half-life and allows for administration once a week. A phase I trial of Pegintron for children and young adults with NF1and PN was completed, and defined the maximum tolerated dose (MTD) as 1 microgram/kg by subcutaneous (SC) injection once weekly for a maximum duration of 2 years. At this dose level, Pegintron was well tolerated, and disease stabilization and minor PN shrinkage by volumetric MRI analysis were observed in several patients. At doses exceeding the MTD fatigue and behavioral changes were dose limiting. A phase II trial of Pegintron will be performed to define the activity of Pegintron for inoperable PN in NF1.
To determine the radiographic and clinical response rate and/or progression free survival of unresectable progressive, or symptomatic (i.e. interfering with performance status), or life threatening NF1 associated PN to Pegintron given weekly SC.
To describe and define the toxicities of Pegintron given weekly SC for prolonged time periods in this patient population.
To compare volumetric analysis of PN using three-dimensional MRI (3-D MRI) to conventional two-dimensional MRI (2-D MRI) and one-dimensional MRI (1-D MRI) data analysis.
To evaluate the effects of Pegintron on serum cytokines and on induction of genes and cytokines in peripheral blood mononuclear cells.
Individuals (greater than or equal to 6 months to 21 years of age) with NF1 and an inoperable plexiform neurofibroma that has the potential to cause significant morbidity.
Patients will be enrolled on one of three strata depending on disease status and age.
Stratum 1: Radiographic progression at trial entry cannot be documented. Patient has no clinical symptoms from the PN. Radiographic response (PN volume decrease greater than or equal to 20 percent) will be the primary endpoint.
Stratum 2: Radiographic progression at trial entry cannot be documented. Patient has clinical symptoms from the PN, such as pain, or decrease in function. Radiographic response (PN volume decrease greater than or equal to 20 percent), and clinical response rate will be the primary endpoint.
Stratum 3: Patient has a progressive PN. Time to progression (TTP) (PN volume increase greater than or equal to 20 percent) will be the primary endpoint, and activity will be defined by comparing TTP on Pegintron to TTP on the placebo arm of the R115777 phase II trial for NF1 PN (01-C-0222) performed at the NCI, POB.
Stratum 4: Age between 6 and 18 months of age and must have a symptomatic and/or life threatening plexiform neurofibroma(s).
Pegintron will be administered SC at a dose of 1.0 mcg/kg/week until disease progression, or development of unacceptable toxicity. In addition, treatment for patients on stratum 1 and 2 will be limited to a maximum of 1 year unless they respond to treatment with Pegintron (partial or complete response), in which case they can continue treatment for a maximum of two years.
Tumor evaluation for volumetric MRI analysis will be performed pre treatment, and prior to months 4, 8, 12, and then after every six months on treatment with Pegintron. Response analysis will be performed centrally at the NCI, POB.
Neurofibromatosis Type 1
Drug: PEG-interferon alfa-2b
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Peginterferon Alpha-2b (PEG-Intron) for Neurofibromatosis Type 1 Related Unresectable, Symptomatic or Life-Threatening Plexiform Neurofibromas|
- Safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Radiographic and clinical response rate and/or progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Toxicity profile [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Efficacy of PEG-Intron [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Evaluate the effects of PEG-Intron on serum cytokines and on induction of genes and cytokines in PBMCs. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Compare volumetric analysis of plexiform neurofibromas using 3D, 2D and 1D MRIs [ Time Frame: 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Drug + Procedure for maximum of 2 years
Drug: PEG-interferon alfa-2b
SC at a dose of 1.0 mcg/kg/week until disease progression, or development of unacce toxicityProcedure: MRI
Pre treatment, and prior to months 4, 8, 12, and then after every six months on treat with PEG-Intron
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00678951
|Contact: Wendy Goodspeed, R.N.||(301) firstname.lastname@example.org|
|Contact: Brigitte C Widemann, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, Pennsylvania|
|Childrens Hospital, Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213-2583|
|Principal Investigator:||Brigitte C Widemann, M.D.||National Cancer Institute (NCI)|