Neurofibromatosis 1
Conditions
Keywords
Neurofibroma, NF-1, Everolimus, mTOR inhibitor
Brief summary
This trial is evaluating the use of oral Everolimus to determine if there is a reduction in the size of the disfiguring cutaneous lesions in patients with Neurofibromatosis 1 over a 6 month period. The evaluation will be done by 3D photography measuring volume with the LIFEVIZ Micro system.
Detailed description
Qualifying subjects will have a diagnosis of Neurofibromatosis 1 and have disfiguring cutaneous lesions that can be measured by photography. The subjects will have photographs of the target lesions,biopsies of the lesions,and safety blood laboratory tests at 3 time points (baseline, 3 months and 6 months which is end of treatment). Everolimus will be taken orally for 6 months. Subjects will visit the clinic monthly for an exam and adverse event evaluation. Laboratory testing will be done at these visits if determined necessary by the PI.
Interventions
DRUGEverolimus
Everyone in the study will receive Everolimus at a starting dose of 10 mg daily and will be adjusted up or down by 2.5 mg at 2 week intervals to attain a trough concentration of 5-15 ng/ml
Sponsors
Texas Neurofibromatosis Foundation
The University of Texas Health Science Center, Houston
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is at least 18 years of age at the time of enrollment 2. Informed consent 3. Compliance with trial requirements (photography, lab draws, medication schedules, and study visits) 4. Diagnosis of NF 1 and has cutaneous neurofibromas that are located in in a region amenable to photography 5. Females of child bearing potential must not be pregnant as confirmed by a negative pregnancy test (blood beta-hCG level) prior to study enrollment and must agree to use appropriate contraceptive methods for the duration of the trial 6. Patient must have adequate liver function as shown by, total bilirubin \</= 2.0 mg/dL, ALT and AST \</= 2.5 X ULN, INR \</= 2 8\. Patient must have adequate renal function, serum creatinine \</= 1.5 X ULN 9. Patient must have adequate lipid profile, fasting serum cholesterol \</= 300 mg/dL OR \</= 7.75 mmol/L, fasting triglycerides \</= X ULN
Exclusion criteria
1\. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.) 2. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus 4. Uncontrolled diabetes mellitus despite adequate therapy 5. Patients who have any severe and /or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction \</= prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease, symptomatic congestive heart failure of New York Hear Association Class III or IV, known active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, or chronic hepatitis, known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), active, bleeding diathesis, chronic treatment with corticosteroids, or other immunosuppressive agents, topical or inhaled corticosteroids are allowed, know history of HIV seropositivity, patients who have received live attenuated vaccines within 1 week of start of Everolimus. Patient would avoid close contact with others who have received live attenuated vaccines during the study, patients who have a history of primary malignancy, with the exceptions of mon-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for \>/- 3 years, patients with a history of non compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study, patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing, pregnant or nursing (lactating) women, women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. highly effective contraception methods,male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3D Photographic Measurement of Surface Volume of Cutaneous Neurofibroma Lesion | 6 months | Photographs of selected lesions to measure surface volume. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3-4 Adverse Events | 6 months | Determination if orally administered Afinitor is safe in patients a indicated by lack of Grade 3-4 adverse events during the trial period. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Determine How Orally Administered Everolimus Effects mTOR Signaling in NF-1 Tissues | 6 months | Quantification via immunohistochemical staining of PTEN, pS6, p4EBP-1, TSC2, mTOR, NF-1, pAKT, VEGF-A and IGF-IR expression in biopsied neurofibroma tissue samples. |
Countries
United States
Participant flow
Pre-assignment details
2 of the 24 enrolled participants withdrew consent immediately and did not receive study drug.
Participants by arm
| Arm | Count |
|---|---|
| Intervention This is a single arm intervention using Everolimus.
Everyone in the study will receive Everolimus at a starting dose of 10 mg daily and will be adjusted up or down by 2.5 mg at 2-week intervals to attain a trough concentration of 5-15 ng/mL. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
3D Photographic Measurement of Surface Volume of Cutaneous Neurofibroma Lesion
Photographs of selected lesions to measure surface volume.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intervention | 3D Photographic Measurement of Surface Volume of Cutaneous Neurofibroma Lesion | Baseline | 32.54 mm^3 |
| Intervention | 3D Photographic Measurement of Surface Volume of Cutaneous Neurofibroma Lesion | 6 months | 33.93 mm^3 |
Secondary
Number of Participants With Grade 3-4 Adverse Events
Determination if orally administered Afinitor is safe in patients a indicated by lack of Grade 3-4 adverse events during the trial period.
Time frame: 6 months
Population: The 2 participants who withdrew consent and did not receive study drug were not analyzed for adverse events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Grade 3-4 Adverse Events | 0 Participants |
Other Pre-specified
Determine How Orally Administered Everolimus Effects mTOR Signaling in NF-1 Tissues
Quantification via immunohistochemical staining of PTEN, pS6, p4EBP-1, TSC2, mTOR, NF-1, pAKT, VEGF-A and IGF-IR expression in biopsied neurofibroma tissue samples.
Time frame: 6 months