Cyclin-Dependent Kinase (CDK)4/6 Inhibitor Abemaciclib for Neurofibromatosis Type I (NF1) Related Atypical Neurofibromas

NCT04750928 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21001121-C-0011
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neurofibromatosis 1

Keywords

Kinase Inhibitor; distinct nodular lesion; genomic alteration

Outcome Measures

Primary Outcomes (1)

• safety of abemaciclib in patients with NF1 and a measurable ANF

  List of adverse event frequency

  30 days after treatment

Secondary Outcomes (6)

• Tolerability of abemaciclib on a prolonged dosing schedule

  up to 2 years of treatment or until disease progression or unacceptable treatment-related toxicity

• Stable disease rate of target ANF

  baseline through 30 days after treatment

• Response rate of non-target ANF/DNL

  at progression

• Effect of abemaciclib on CDK4/6 target inhibition

  after Day 7 of Cycle 1

• Effect of abemaciclib on ANF related pain and quality of life

  baseline through 30 days after treatment

Study Arms (2)

1/ Phase I Dose Escalation

EXPERIMENTAL

Abemaciclib orally twice daily at escalating doses to determine the MTD/RP2D

Drug: Abemaciclib

2/ Phase II Objective Response Rate

EXPERIMENTAL

Abemaciclib orally twice daily at the RP2D

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Abemaciclib is to be administered orally on Days 1 through 28 of each 28-day cycle

1/ Phase I Dose Escalation; 2/ Phase II Objective Response Rate

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants
• Participants must have a clinical diagnosis of NF1, i.e., participants must have at least two of the diagnostic criteria for NF1 or a confirmed NF1 mutation from a CLIA-certified laboratory:
• 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
• Optic glioma
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A first-degree relative with NF1
• Measurable disease: Participants must have at least one measurable ANF defined as a lesion of at least 3 centimeters (cm) measured in one dimension. Measurability and suitability for volumetric MRI analysis of the target ANF must be confirmed with the NCI POB prior to enrolling a participant. The target ANF will be defined as the clinically most relevant ANF, which has to be amenable to volumetric MRI analysis.
• Prior Therapies:
• Since there is no standard effective chemotherapy for patients with NF1 and ANF, participants may be treated on this trial without having received prior medical therapy directed at their ANF.
• Investigational agents/biologic therapies (not chemotherapy): Participants who have received previous investigational agents or biologic therapies are eligible for enrollment. At least 30 days or 5 half-lives must have elapsed since receiving medical therapy directed at any NF1 related tumor. Participants who received prior medical therapy for a NF1 related tumor manifestation must have recovered from the acute toxic effects of all prior therapy to grade 1 CTCAEv5 except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment before entering this study.
• Chemotherapy agents: Participants who received chemotherapy must have recovered (CTCAE Grade \<=1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 28 days is required between last chemotherapy dose and enrollment (provided the participant did not receive radiotherapy).
• Participants who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. Participants who have received previous radiation therapy are eligible for enrollment. At least 6 weeks must have elapsed since the last radiation therapy and start of treatment. The only target ANF cannot have received radiation previously.

You may not qualify if:

• 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.
• Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Participants with HIV who have adequate CD4 counts and who have no requirement for antiviral therapy will be eligible.
• NOTE:Screening is not required for enrollment.
• Participants with interstitial lung disease
• Requires treatment with strong CYP3A inhibitors or inducers
• Inability to swallow tablets, since tablets cannot be crushed or broken.
• Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol. Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target ANF on MRI.
• Refractory nausea and vomiting that would limit drug administration in the opinion of the Principal Investigator
• Known severe hypersensitivity to abemaciclib or any excipient of abemaciclib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib
• Clinical judgment by the investigator that the participant should not participate in the study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibromatosis 1

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda M Carbonell

CONTACT

(240) 760-6006; amanda.carbonell@nih.gov

Brigitte C Widemann, M.D.

CONTACT

(240) 760-6203; widemanb@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 11, 2021
• Study Start: November 29, 2021
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 24, 2026

Record last verified: 2025-12-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)