Background:
NF1 is a genetic disease that causes tumors called atypical neurofibromas. These tumors, which arise from nerves, can cause serious medical problems. The only treatment is surgery. Researchers want to see if a drug called abemaciclib can help.
Objective:
To find a safe, tolerable dose of abemaciclib for treating atypical neurofibromas.
Eligibility:
People ages 12 and older who have NF1 and have one or more atypical neurofibromas that cannot or will not be removed with surgery
Design:
Participants will be screened with:
Medical history and physical exam
Blood, urine, and heart tests
MRI: Participants will lie in a machine that takes pictures of the body. A padding or coil will be placed around their head. They may have a contrast agent injected into a vein.
Biopsy sample: A small piece of tumor will be removed using a large needle.
Participants will have frequent visits during the study. These will include repeats of the screening tests as well as the following:
PET scan: Participants will lie in a machine that takes pictures of the body. They will have a contrast agent injected into their arm.
Questionnaires about the effects of abemaciclib on pain and quality of life
Possible photographs of tumors
Participants will take abemaciclib capsules orally twice daily in 28-day cycles. They will take the drug for up to 2 years. Some may be able to take it for longer.
Participants will have a follow-up visit about 30 days after their last dose of the study drug. Then they will have visits every 3 months for 1 year.
All Participants
Six or more caf(SqrRoot)(Copyright)-au-lait macules (>= 0.5cm in prepubertal participants or >= 1.5 cm in post pubertal participants)
Freckling in axilla or groin
A neurofibroma or plexiform neurofibroma
Pregnant women, or women who intend to become pregnant during the study, are excluded from this study because of the teratogenic effects of abemaciclib. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study.
May not have a NF1-related tumor such as optic pathway glioma or malignant peripheral nerve sheath tumor, which requires treatment with chemotherapy or surgery.
Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel that would preclude adequate absorption, or preexisting Crohn s disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, or psychiatric illness/social situations that would limit compliance with study requirements.
Sequential
Abemaciclib
DrugAbemaciclib is to be administered orally on Days 1 through 28 of each 28-day cycle
safety of abemaciclib in patients with NF1 and a measurable ANF
List of adverse event frequency
Tolerability of abemaciclib on a prolonged dosing schedule
Duration of treatment and adverse event types and frequency
Stable disease rate of target ANF
Proportion of patients that have progressive disease
Response rate of non-target ANF/DNL
Changes in non-target ANF/DNL determined by volumetric MRI analysis
Effect of abemaciclib on CDK4/6 target inhibition
Measurement of phosphorylated Retinoblastoma (pRB) in tumor biopsy samples
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