Plexiform Neurofibroma
Conditions
Brief summary
This study is for slow growing tumors called plexiform neurofibromas (PNF) which are a relatively common problem in people with neurofibromatosis type 1 (NF1). These tumors are benign but as they grow, they can become disfiguring as well as disabling or even life threatening. They often cause pain, difficulty using arms or legs because of spinal cord compression, and/or nerve damage. At present, the only available therapy for plexiform neurofibromas is to try to surgically remove as much of the tumor as is possible. Because these tumors grow into the surrounding areas, total surgical resection is often impossible. Most tumors will re-grow after surgery if the entire tumor cannot be removed. To date, other treatments including chemotherapy and radiotherapy have not been able to shrink these tumors. Interferon is a drug that is used for different types of tumors as well as for hepatitis. It has been used in the treatment of plexiform neurofibromas (PNF) with some subjects showing improvement in symptoms and/or a decrease in the size of the tumor. Most subjects had no further growth of their tumor while on the PEG-Intron. The drug used in this study is PEG (pegylated)-Intron. PEG-Intron is a long acting form of interferon which keeps the drug from being broken down in the body for a longer period of time and potentially could be more effective than the short-acting interferon. PEG-Intron has been approved by the Food and Drug Administration (FDA) for the treatment of Hepatitis C. The goals of this study are: 1. To determine how your child's plexiform neurofibroma responds to PEG-Intron when given weekly. 2. To determine the side effects of PEG-Intron when given weekly to participants with plexiform neurofibromas. 3. To evaluate a new method of measuring changes in the size of tumors called volume analysis. This method measures the entire volume of a tumor in three dimensions. The standard method of measuring tumors uses only the length and/or width of the tumor. By studying the different ways of measuring tumors the investigators hope to be able to determine which method is the most accurate and useful.
Detailed description
PEG-Intron will be given every week through a small needle under the skin, in the same way that insulin is given to people with diabetes. Subjects will be taught to do this at home. As long as the tumor isn't growing and the side effects are tolerable, the injections will be given once a week for 2 years. Children will be enrolled on the study into one of three strata (patient groups): strata 1 includes children who do not have any symptoms associated with their PNF and MRI scans over the past year may or may not show tumor growth, strata 2 includes children who have symptoms associated with the PNF but MRI scans over the past year have not shown growth and strata 3 includes children who have shown an increase in the size of the PNF on MRI scans over the past year, with or without any symptoms.
Interventions
DRUGPEG-Intron
Sponsors
National Cancer Institute (NCI)
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 21 Years
Healthy volunteers
No
Inclusion criteria
* Age \> or equal to 18 months to 21 years * Diagnosis Patients with NF1 and progressive, symptomatic or life-threatening plexiform neurofibromas which are not surgically resectable. Patients without biopsy-proof of plexiform must have at least one other diagnostic criteria for NF1: 6 or more cafe-au-lait spots, freckling in the axilla or groin, optic glioma, 2 or more Lisch nodules, distinctive bony lesion, first degree relative with NF1. * Only eligible if complete tumor resection is not feasible, or if a patient with a surgical option refuses surgery. * Patients may be treated on this trial without having received prior therapy. If patients have received prior therapy, they must have recovered from all toxic effects prior to entering this study. * Must have life expectancy of at least 12 months and a performance score (Karnofsky or Lansky) of \> or equal to 50. * Must have adequate liver, kidney and bone marrow function
Exclusion criteria
* Clinically significant unrelated systemic illness. * Received an investigational agent within the past 30 days. * Evidence of active visual pathway glioma * History of malignant peripheral nerve sheath tumor or ther cancer other than surgically cured non-melanoma skin cancer or cervical carcinoma in situ * Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, or immunotherapy. * Inability to return for follow-up visits or obtain follow-up studies * Severe cardiovascular disease * Pre-existing sever psychiatric condition or history of psychiatric disorder requiring hospitalization or a history of suicidal ideation or attempt. * Thyroid dysfunction not responsive to therapy. * Uncontrolled diabetes mellitus * History of seropositivity for HIV * Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception. * Any medical condition requiring chronic systemic corticosteroids. * Subjects who are known to be actively abusing alcohol or drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Imaging Response in Strata 1 and 2 | MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study. | A response was defined as a ≥20% reduction in the sum of the volume of the target plexiform neurofibroma ( PN) within 12 months confirmed by a follow-up MRI after ≥4 weeks. |
| Clinical Response in Stratum 2 | baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study | Clinical response was defined as a protocol-specified improvement in ophthalmologic evaluation, an improvement of at least one level in performance status (PS) ≥50% decrease in the amount of pain medications required per week compared with baseline or ability to change from a narcotic to a nonnarcotic analgesic, sustained for at least one month. |
| Time to Progression (TTP) in Stratum 3 | baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study | TTP was estimated by the Kaplan-Meter method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Imaging Response in Stratum 3 | MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study | A Response was defined as a ≥ 20% reduction in the sum of the volume of the target plexiform neurofibroma (PN) within 12 months, confirmed by a follow-up MRI after ≥ 24 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1 No Symptom With or Withour Tumor Growth Peg-intron given every week | 27 |
| Stratum 2 Symptoms no Tumor Growth Peg-intron given every week | 26 |
| Stratum 3 Tumor Growth With or Without Symptoms Peg-intron given every week | 29 |
| Total | 82 |
Baseline characteristics
| Characteristic | Total | Stratum 1 No Symptom With or Withour Tumor Growth | Stratum 2 Symptoms no Tumor Growth | Stratum 3 Tumor Growth With or Without Symptoms |
|---|---|---|---|---|
| Age, Customized 5 to 12 years | 31 Participants | 10 Participants | 9 Participants | 12 Participants |
| Age, Customized greater than or equal to 12 years | 30 Participants | 14 Participants | 8 Participants | 8 Participants |
| Age, Customized Less than 5 years | 20 Participants | 3 Participants | 8 Participants | 9 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment United States | 82 participants | 27 participants | 26 participants | 29 participants |
| Sex: Female, Male Female | 0 Participants | — | — | — |
| Sex: Female, Male Male | 0 Participants | — | — | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 26 | 0 / 29 |
| other Total, other adverse events | 7 / 27 | 8 / 26 | 6 / 29 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 0 / 29 |
Outcome results
Primary
Clinical Response in Stratum 2
Clinical response was defined as a protocol-specified improvement in ophthalmologic evaluation, an improvement of at least one level in performance status (PS) ≥50% decrease in the amount of pain medications required per week compared with baseline or ability to change from a narcotic to a nonnarcotic analgesic, sustained for at least one month.
Time frame: baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study
Population: Only participants in Stratum 2 contributed data for this Outcome Measure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum 1 No Symptom With or Withour Tumor Growth | Clinical Response in Stratum 2 | 3 participants |
Primary
Number of Participants With Imaging Response in Strata 1 and 2
A response was defined as a ≥20% reduction in the sum of the volume of the target plexiform neurofibroma ( PN) within 12 months confirmed by a follow-up MRI after ≥4 weeks.
Time frame: MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 No Symptom With or Withour Tumor Growth | Number of Participants With Imaging Response in Strata 1 and 2 | Confirmed Response | 0 participants |
| Stratum 1 No Symptom With or Withour Tumor Growth | Number of Participants With Imaging Response in Strata 1 and 2 | Unconfirmed Response | 1 participants |
| Stratum 2 Symptoms no Tumor Growth | Number of Participants With Imaging Response in Strata 1 and 2 | Confirmed Response | 1 participants |
| Stratum 2 Symptoms no Tumor Growth | Number of Participants With Imaging Response in Strata 1 and 2 | Unconfirmed Response | 0 participants |
Primary
Time to Progression (TTP) in Stratum 3
TTP was estimated by the Kaplan-Meter method
Time frame: baseline, week 6, months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study
Population: Only participants in Stratum 3 contributed data for this Outcome Measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 No Symptom With or Withour Tumor Growth | Time to Progression (TTP) in Stratum 3 | 29.4 months |
Secondary
Number of Participants With Imaging Response in Stratum 3
A Response was defined as a ≥ 20% reduction in the sum of the volume of the target plexiform neurofibroma (PN) within 12 months, confirmed by a follow-up MRI after ≥ 24 weeks
Time frame: MRI scans were performed at baseline and at months 4, 8, 12, 18, and 24 while on treatment and every 6 months thereafter until off study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stratum 1 No Symptom With or Withour Tumor Growth | Number of Participants With Imaging Response in Stratum 3 | Confirmed Response | 1 participants |
| Stratum 1 No Symptom With or Withour Tumor Growth | Number of Participants With Imaging Response in Stratum 3 | Unconfirmed Response | 1 participants |