Pegintron to Treat Plexiform Neurofibromas in Children and Young Adults
- Neurofibromatosis type I (NF1) is a genetic disease that results in the development of several types of tumors, including plexiform neurofibromas, tumors that involve a nerve and its branches.
- Surgical removal of all plexiform neurofibromas is not always possible because of the number or location of the tumors. There are no known medical treatments for the tumors.
- Peginterferon alfa-1b (Pegintron) is a sustained-release form of the drug interferon alfa-2b, which has caused tumor shrinkage in some patients with various types of cancer. It is approved by the Food and Drug Administration to treat hepatitis C.
- To determine if Pegintron can shrink or slow the growth of plexiform neurofibromas in children and young adults, or reduce pain or other problems they cause.
- To determine the side effects of Pegintron in children and young adults.
- To compare three methods of measuring plexiform neurofibromas.
- To evaluate the effect of Pegintron on blood proteins and expression of genes in gene blood cells.
-Patients between 18 months and 21 years of age with NF1 and an inoperable plexiform neurofibroma that can cause serious medical problems.
- Patients receive Pegintron by injection under the skin once a week for up to 1 year in 4-week treatment cycles as long as their tumor continues to grow and the drug is well tolerated. Patients who show benefit may extend treatment for another year.
During the study, patients undergo the following tests and evaluations:
- Physical examination before starting treatment, at 6 and 12 weeks after treatment, then every 4 months for the first year and every 6 months the second year.
- Blood tests before starting treatment, at 6 and 12 weeks after treatment, then every 4 months for the first year and every 6 months the second year to evaluate treatment side effects.
- Blood tests before starting treatment and after 4 months of treatment to evaluate the effects of Pegintron on blood proteins and expression of genes in the blood cells.
- MRI before starting treatment, then at 4, 8, 12, 18 and 24 months.
- Eye examinations in patients with orbital tumors before starting treatment, then at 4, 8, 12, 18 and 24 months.
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|
- Radiographic response (stratum 1) [ Designated as safety issue: No ]
- Radiographic and clinical response (stratum 2) [ Designated as safety issue: No ]
- Progression-free survival (stratum 3) [ Designated as safety issue: No ]
- Clinical and radiographic response (stratum3) [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Strata 1 and 2
Patients receive PEG-interferon alfa-2b subcutaneously once a week for 4 weeks. Courses repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients who achieve a partial or complete response may continue treatment for up to 2 years.
Drug: PEG-interferon alfa-2b
Experimental: Straum 3
Patients receive PEG-interferon alfa-2b as in strata 1 and 2. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: PEG-interferon alfa-2b
Hide Detailed Description
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00678951
|Contact: Wendy Goodspeed, R.N.||(301) email@example.com|
|Contact: Brigitte C Widemann, M.D.||(301) firstname.lastname@example.org|
|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)|