Nfm-01. Nf105: a Phase Ii Prospective Study of Cabozantinib (xl184) for Plexiform Neurofibromas in Subjects With Neurofibromatosis Type 1: a Neurofibromatosis Clinical Trial Consortium (nfctc) Study
Year: 2018
Type: conference-abstract
Abstract: Plexiform neurofibromas (PNs) are histologically complex peripheral nerve sheath tumors composed of Schwann cells and fibrocytes. Pre-clinical models have demonstrated that altering the microenvironment with molecular targeting therapy may lead to the shrinkage of PN. Here we test the activity of Cabozantinib, a tyrosine kinase inhibitor of KIT, MET, VEGF, and AXL, in adolescents and adults with NF1-associated PN. The NFCTC conducted a study (NCT02101736) evaluating Cabozantinib in subjects ≥16 years with clinically significant PN. Response was determined by MRI assessment of tumor volume. Cabozantinib was administered daily on a continuous dosing schedule for up to 2 years. Starting dose was 40 mg oral daily dose with a dose escalation to 60 mg. Success was determined as ≥ 25% of subjects achieving and maintaining ≥ 20% decrease in tumor volume. 19 evaluable subjects were assessed with a mean age of 23. Subjects were evaluable if they completed at least 1 cycle of therapy and had at least one follow-up tumor imaging. 4 subjects were not evaluable due to enrollment error (n=2), withdrawal during cycle 1 (n=1), ineligible due to eligibility exclusions (n=1). Eight patients (42%) met criteria for PR by 1 year. No subjects had PN progression. Common toxicities were gastrointestinal, hypothyroidism, fatigue, headaches, skin and leukopenia. Three subjects experiencing grade 3 SAEs remained on study after dose reductions. Cabozantinib demonstrated activity and was well tolerated in patients with clinically significant PN. This trial will be expanded to include a cohort of children <16 years.
Source: Neuro-Oncology
Institutions: Indiana University Indianapolis, Johns Hopkins University, National Cancer Institute, University of Alabama at Birmingham, Boston Children's Hospital, New York University, Children's National, Comer Children's Hospital, Washington University in St. Louis, Massachusetts General Hospital, Children's Hospital of Los Angeles, Children's Hospital of Philadelphia
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2809615788